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Dissertations / Theses on the topic 'Paracrine'
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Petersen, Cecilia. "Paracrine regulation of Sertoli cell proliferation /." Stockholm, 2003. http://diss.kib.ki.se/2003/91-7349-443-7/.
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Renshaw, Derek. "Paracrine regulation of the rat adrenal gland." Thesis, Queen Mary, University of London, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.251614.
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Luke, Garry A. "Paracrine signals of the endometrium and trophoblast." Thesis, University of Aberdeen, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.327971.
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Both the endometrium and the trophoblast secrete a number of proteins. Some of these, e.g. human chorionic gonadotrophin (hCG) from the trophoblast and pregnancy-associated endometrial α2-globulin (α2-PEG) from the endometrium, are secreted into the bloodstream and may act as endocrines. Moreover, they may also function as paracrines, signalling to adjacent tissues. Several models have been developed, by which the paracrine activity of the endometrium and the trophoblast might be examined <i>in vitro</i>. These include, cultures of endometrium and trophoblast, dual chamber superfusion of membranes and dual perfusion of individual placental cotyledons. The purpose of the present study was to examine some aspects of experimental design on the results from these models and consider the factors that might govern the rate of release. A good many trophoblast proteins have been characterised and methods devised for their quantitative measurement, however, the study of endometrial proteins is less advanced. As a first step, a method was developed for the measurement of α2-PEG, the major secretory protein of the secretory endometrium during the first trimester of pregnancy. This thesis describes the development of a competitive ELISA for measuring α2-PEG. This assay was employed for measuring α2-PEG in the medium from decidual cultures. In this thesis, release of protein <i>in vitro</i> has been examined as a mode of basal unstimulated secretion <i>in vivo</i>. The release is compounded of at least two simultaneous processes, biosynthesis and the transport of formed material to the outside of the cell. The concept is put forward that protein release is determined by a dynamic balance between biosynthesis of new protein and diffusion of protein down the concentration gradient between cell cytoplasm and the surrounding medium.
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Smith, Katherine Sue. "Autocrine/paracrine regulation of ATP citrate lyase /." The Ohio State University, 1990. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487683401444039.
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Rajapakse, Niwanthi W. "Paracrine factors and regulation of regional kidney perfusion." Monash University, Dept. of Physiology, 2004. http://arrow.monash.edu.au/hdl/1959.1/9589.
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Renlund, Nina. "Hormonal and paracrine influences on Leydig cell steroidogenesis /." Stockholm, 2006. http://diss.kib.ki.se/2006/91-7140-842-8/.
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Tamiya, Shigeo. "Autocrine and paracrine signalling mechanisms in lens cells." Thesis, University of East Anglia, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.365025.
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Bent, Eric Huttenlocher. "Mechanisms of microenvironmental paracrine signaling in cancer chemoresistance." Thesis, Massachusetts Institute of Technology, 2016. http://hdl.handle.net/1721.1/104167.
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Thesis: Ph. D., Massachusetts Institute of Technology, Department of Biology, 2016.<br>Cataloged from PDF version of thesis.<br>Includes bibliographical references.<br>Chemoresistance remains a major barrier to the effective treatment of cancer. Cancer therapy occurs in the context of a tissue environment, with cancer cells surrounded by many non-malignant cells that contribute to tumor growth and resistance to therapy. Yet much remains unknown about the tumor microenvironment and its impact on therapeutic response. The specific cell types and microenvironment factors that influence chemoresistance, how therapy induced damage of the microenvironment changes these factors and the mechanisms by which the microenvironment contributes to therapy failure remain incompletely understood. To study microenvironment signaling and its impact on therapy response, I have used mouse models of B-cell leukemia and lymphoma. I find that the chemotherapeutic doxorubicin promotes endothelial IL-6 release through reactive oxygen species-mediated p38 signaling and use tissue specific knockout mice to demonstrate that endothelial-specific production of IL-6 promotes lymphoma chemoresistance in vivo. Doxorubicin induces endothelial-cell senescence, an irreversible growth arrest typically accompanied by a robust secretory response. I show that P13K/AKT/mTOR signaling is repressed in senescent endothelial cells and serves as switch, turning off chronic senescence-associated IL-6 production. These data implicate endothelial paracrine signaling in the promotion of chemoresistance and elucidates the molecular control of acute vs. chronic therapy-induced cytokine secretion. Conventional chemotherapeutics such as doxorubicin can induce anti-cancer immune responses through the promotion of an immunogenic form of cell death. However, these responses are normally repressed by the microenvironment, impairing therapeutic response. I demonstrate that microenvironment IL-6 inhibits the generation of anti-leukemia immunity after immunogenic chemotherapy and find that CD8+ T-cell responses cure the majority of IL-6-/- mice treated with immunogenic chemotherapy. IL-6 also inhibits the efficacy of immune checkpoint blocking agents, implicating it as a promising target to improve the generation of anti-cancer immunity. Thus, the work in this thesis identifies the molecular control of therapy induced endothelial paracrine signaling and identifies a key role for IL-6 in suppressing anti-cancer immune responses induced by therapy.<br>by Eric Huttenlocher Bent.<br>Ph. D.
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Smyth, Christopher David. "Paracrine mechanisms of gonadotrophin action on the ovary." Thesis, University of Edinburgh, 1994. http://hdl.handle.net/1842/20805.
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This thesis describes a study of the role of local regulators in the modulation of gonadotrophin action. It was found that <I>in vivo</I> FSH stimulated granulosa cell proliferation and increased ovarian weight, but was incapable of stimulating granulosa cells to proliferate <I>in vitro</I>. This suggests that the action of FSH <I>in vivo</I> is mediated through another factor. However, in the presence of LH, FSH also stimulated the expression of differentiated functions (progesterone and oestradiol production) both <I>in vivo</I> and <I>in vitro</I> demonstrating a direct effect of FSH. In the absence of LH or aromatase substrate, FSH induced the potential for aromatisation but did not increase uterine weight, a marker of oestradiol production. Therefore it is concluded that FSH is the primary stimulus for follicular development but that LH is also required for co-ordinated follicular development. There is a growing body of indirect evidence to suggest that factors of FSH-stimulated granulosa cell origin may regulate adjacent thecal/interstitial cells. Cytochrome P45017α (17-hydroxylase/C<SUB>17-20</SUB> lyase) in thecal/interstitial cells is a LH-responsive steroidogenic enzyme vital for androgen production. To obtain direct evidence for FSH-stimulated paracrine signalling in the ovary a rat thecal/interstitial cell culture system was validated for the study of the control of androgen production. Using this system and Northern hybridisation the control of androgen production by gonadotrophins and granulosa cell derived factors was studied. The 2.0 kb P45017α mRNA signal in ovarian total RNA from intact animals was dose-dependently increased by treatment with recombinant human FSH (rh-FSH). Treatment of hypophysectomised animals with rh-FSH did not consistently alter ovarian P45017α mRNA levels, though in the presence of low levels of LH, FSH increased P45017α mRNA expression.
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Sjöblom, Tobias. "Paracrine and autocrine functions of PDGF in malignant disease." Doctoral thesis, Uppsala University, Ludwig Institute for Cancer Research, 2002. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-2678.
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<p>Growth factors and their receptors are frequently activated by mutations in human cancer. Platelet-derived growth factor (PDGF)-B and its tyrosine kinase receptor, the PDGF β-receptor, have been implicated in autocrine transformation as well as paracrine stimulation of tumor growth. The availability of clinically useful antagonists motivates evaluation of PDGF inhibition in these diseases.</p><p>In chronic myelomonocytic leukemia with t(5;12), parts of the transcription factor TEL and the PDGF β-receptor are fused, generating a constitutively signaling protein. Oligomerization and unique phosphorylation pattern of TEL-PDGFβR was demonstrated, as well as the transforming activity of TEL-PDGFβR, which was sensitive to PDGF β-receptor kinase inhibition.</p><p>Dermatofibrosarcoma protuberans (DFSP) is characterized by a translocation involving the collagen Iα1 and PDGF B-chain genes. The COLIA1-PDGFB fusion protein was processed to mature PDGF-BB and transformed fibroblasts in culture. The PDGF antagonist STI571 inhibited growth of <i>COLIA1-PDGFB</i> transfected cells and primary DFSP cells <i>in vitro</i> and <i>in vivo</i> through induction of apoptosis.</p><p>Paracrine effects of PDGF-DD, a ligand for the PDGF β-receptor, were evaluated in a murine model of malignant melanoma. PDGF-DD production accelerated tumor growth and altered the vascular morphology in experimental melanomas.</p><p>A validated immunohistochemical procedure for PDGF β-receptor detection was established and applied to normal tissues and more than 280 tumor biopsies. Perivascular and stromal expression was detected in 90% and 50%, respectively, of human tumors.</p><p>Recently, non-transformed cells in the tumor microenvironment have emerged as targets in cancer therapy. Selective sensitization of tumor fibroblasts to paclitaxel by STI571 was evaluated <i>in vitro</i> and in a xenograft model. Whereas neither drug alone caused growth inhibition, combination of the two significantly reduced tumor growth, suggesting anti-stromal therapy as a possible treatment modality in solid tumors.</p>
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Bradshaw, Clare Louise. "Autocrine and paracrine growth mechanisms in human B lymphocytes." Thesis, University of Glasgow, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.300653.
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Tschirhart, Eric. "Regulation paracrine de la contactilite du muscle lisse bronchique." Université Louis Pasteur (Strasbourg) (1971-2008), 1988. http://www.theses.fr/1988STR13194.
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Tschirhart, Eric. "Régulation paracrine de la contractilité du muscle lisse bronchique." Grenoble 2 : ANRT, 1988. http://catalogue.bnf.fr/ark:/12148/cb37618990s.
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Kumar, Veena A. "A paracrine/autocrine role of prostaglandins in adipose tissue development." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk2/tape16/PQDD_0009/MQ28431.pdf.
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Cabrera, Over. "Autocrine/paracrine interactions modulating hormone release in the endocrine pancreas /." Stockholm : Karolinska institutet, 2007. http://diss.kib.ki.se/2007/978-91-7357-378-8/.
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Chandras, Christina. "Novel paracrine/autocrine roles of prostaglandins in the human ovary." Thesis, University College London (University of London), 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.396224.
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Lee, Christopher S. D. "Directing the paracrine actions of adipose stem cells for cartilage regeneration." Diss., Georgia Institute of Technology, 2012. http://hdl.handle.net/1853/44713.
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Current cartilage repair methods are ineffective in restoring the mechanical and biological functions of native hyaline cartilage. Therefore, using the paracrine actions of stem cell therapies to stimulate endogenous cartilage regeneration has gained momentum. Adipose stem cells (ASCs) are an attractive option for this endeavor because of their accessibility, chondrogenic potential, and secretion of factors that promote connective tissue repair. In order to use the factors secreted by ASCs to stimulate cartilage regeneration, the signaling pathways that affect postnatal cartilage development and morphology need to be understood. Next, approaches need to be developed to tailor the secretory profile of ASCs to promote cartilage regeneration. Finally, delivery methods that localize ASCs within a defect site while facilitating paracrine factor secretion need to be optimized.
The overall objective of this thesis was to develop an ASC therapy that could be effectively delivered in cartilage defects and stimulate regeneration via its paracrine actions. The general hypothesis was that the secretory profile of ASCs can be tailored to enhance cartilage regeneration and be effectively delivered to regenerate cartilage in vivo. The overall approach used the growth plate as an initial model to study changes in postnatal cartilage morphology and the molecular mechanisms that regulate it, different media treatments and microencapsulation to tailor growth factor production, and alginate microbeads to deliver ASCs in vivo to repair cartilage focal defects.
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Cao, Yu. "Morphological and functional characterization of the neurotransmitter GABA in adult rat taste buds." Columbus, Ohio : Ohio State University, 2006. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1141853118.
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Myers, Michelle. "In vitro modelling of paracrine and endocrine interactions in the human ovary." Thesis, University of Edinburgh, 2008. http://hdl.handle.net/1842/29292.
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Women with regular cycles having hysterectomy for non-malignant conditions and women undergoing oocyte retrieval for assisted conception were used in the current study. Novel primary cultures and co-cultures of lutinised granulosa cells and fibroblast-like cells allowed the mechanistic <i>in vivo</i> interactions of the corpus luteum to be mimicked with an <i>in vitro</i> system. Herein, activin A is identified as a regulated molecule that may promote tissue remodelling during luteolysis. Activin A is secreted by luteal steroidogenic cells and at physiological concentrations it up regulates MMP-2 activity and expression in luteal fibroblast-like cells. HCG can inhibit activin A through several mechanisms including up regulating activin inhibitors, inhibin A and follistatin. Results suggest that activin is an excellent anti-luteal molecule whose paracrine/endocrine actions are to remove or potentially inhibit luteal tissue formation, and moreover to facilitate human luteolysis. However, the biological actions of activin A are inhibited during maternal recognition of pregnancy in the presence of conceptus-derived hCG which has marked and disparate changes on surrounding cell types that do not expression the hCG receptor. Consequently, luteolysis is presented, such that luteal fibroblast-like MMP-2 is inhibited as hCG-derived cortisol production promotes the maternal recognition of pregnancy.
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Wijngaarden, Jan van. "Ace inhibitors and cardiovascular regulation the importance of autocrine and paracrine mechanisms /." [S.l. : [Groningen : s.n.] ; University Library Groningen] [Host], 1992. http://irs.ub.rug.nl/ppn/298212978.
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Colón, Eugenia. "Autocrine and paracrine regulation of Leydig cell survival in the postnatal testis /." Stockholm : Karolinska institutet, 2007. http://diss.kib.ki.se/2007/978-91-7357-275-0/.
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Poole, Charla N. "Cardiovascular therapeutics derived from the paracrine biology of adult human progenitor cells." Thesis, Tulane University, 2014. http://pqdtopen.proquest.com/#viewpdf?dispub=3628932.
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<p> Adult multipotent stromal cells (MSCs) may repair tissue through the action of secreted factors on endogenous stem/progenitor cells. We determined the effects of MSC-secreted factors on adult cardiac progenitor cells (CPCs). Serum-free conditioned medium (CdM) was collected from MSCs isolated by plastic adherence (MSCs) and by magnetic sorting against the p75 nerve-growth factor receptor (p75MSCs). Compared to serum-free medium (α-MEM), CdM significantly increased adult rat CPC proliferation in a concentration-dependent manner, led to phosphorylation (Tyr<sup>705</sup>) and nuclear localization of signal transducer and activator of transcription 3 (STAT3) and was blocked by both AG490, a Janus kinase 2 (Jak2)/STAT3 inhibitor, and Stattic, a specific STAT3 (Tyr<sup>705</sup>) inhibitor. Also signaling through Jak2/STAT3, MSC CdM cytoprotective factors significantly increased survival of hypoxic CPCs compared to α-MEM. Intra-arterial infusion of p75MSC CdM 24 hours after myocardial infarction (MI) in mice significantly reduced myocardial necrosis at 48 hours after MI compared to α-MEM (vehicle). Echocardiography at 1 week after MI demonstrated significantly better cardiac function in p75MSC CdM-treated mice compared to controls. Thus <i>in vivo</i> benefits of MSCs may be derived in part by the action of their secreted factors on CPCs. </p><p> Epicardial-derived cells are required for cardiac development, support myogenesis through secreted factors and participate in repair and remodeling after injury. We tested whether factors secreted by epicardial-derived precursor cells (EPDCs) would protect jeopardized ischemic myocardium after myocardial infarction and reperfusion (MI-I4R). Human epicardial progenitor cells, isolated from right atrial appendages removed during cardiac bypass surgery, were keratin-positive, epithelial in morphology and expressed TFs associated with pro-epicardium, epicardium and cardiac development. Upon progenitor cell epithelial-mesenchymal transition (EMT) into EPDCs, concentrated conditioned medium (EPI CdM) was generated. When compared to á-MEM (vehicle), intra-arterial infusion of human EPI CdM led to a reduction in infarct size of 50% in both immunodeficient and immunocompetent MI-I4R mice and improved cardiac function. These <i> in vivo</i> results were evident as early as 24 hours after MI, sustained for at least 1 month, and may derive in part through paracrine protection of jeopardized coronary microvasculature. Our results indicate that EPI CdM or a combination of its ligands may provide an effective treatment for MI.</p>
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Cadranel, Jacques. "1,25 (OH) 2d3 médiateur endocrine et paracrine au cours des granulomatoses pulmonaires." Paris 5, 1993. http://www.theses.fr/1993PA05CD03.
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Dans ce travail, nous montrons tout d'abord une production de 1,25 (OH)2D3 par les cellules pulmonaires fraîchement recueillies par lavage bronchoalvéolaire (LBA) chez des sujets tuberculeux hypercalcémiques (annexe I). Ensuite, après avoir constaté une corrélation entre les capacités de production de la 1,25 (OH)2D3 par ces cellules alvéolaires et les anomalies du bilan phosphocalciques (annexe II), nous avons identifié les cellules responsables de cette production chez des sujets tuberculeux non hypercalcémiques (annexe III). Ainsi, nous avons montré qu'une activité 25(OH)D3-1-a-hydroxylase est toujours retrouvée dans les macrophages T pulmonaires alors qu'elle est inconstante dans les macrophages et paraît absente ou considérablement réduite dans les cellules circulantes. Parallèlement, nous avons montré qu'une fraction des lymphocytes T alvéolaires expriment le récepteur de la 1,25 (OH)2D3 au site de la tuberculose, récepteur absent des lymphocytes circulants (annexe IV). La poursuite de notre recherche dans ce domaine vise à apprécier les interactions entre la 1,25 (OH)2D3 et les cellules (lymphocytes, monocytes) produisant des médiateurs impliqués dans la formation et la régulation des activités du granulome (TNFa, PGE2, IGF1, gIFN. . . ) (annexes V-VII).
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Xie, Ming. "Additive effects among uterine paracrine factors in promoting bovine trophoblast cell proliferation." Thesis, Virginia Tech, 2014. http://hdl.handle.net/10919/79562.
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Several uterine-derived paracrine factors have been implicated as critical regulators of conceptus development in cattle, but it remains unclear how these factors work together to establish and maintain pregnancies. The primary objectives of this work were to establish if cooperative interactions between epidermal growth factor (EGF), fibroblast growth factor-2 (FGF2) and insulin-like growth factor-1 (IGF1) promote bovine trophoblast cell proliferation, and to decipher the intracellular signaling mechanisms employed by these growth factors to regulate cell proliferation. Pilot studies established effective concentrations for each growth factor on a bovine trophoblast cell line (CT1). The first set of studies examined how each factor worked individually or in conjunction with each other to impact CT1 proliferation. Mitotic index (percentage of EdU-positive nuclei after a 45 min challenge) was increased (P<0.05) by supplementation with 10 ng/ml EGF, 10 ng/ml FGF2, or 50 ng/ml IGF1 when compared with non-treated controls. In addition, a greater increase (P<0.05) was detected when all three factors were supplemented together. A follow-up study determined that supplementation of any two growth factors could not replicate the cooperative effect noted when all three factors were provided. A second set of studies was undertaken to examine how mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase/AKT (PI3K/AKT) signaling systems mediate the independent and cooperative effects of these paracrine factors. Both EGF and IGF1 transiently activated mitogen-activated protein kinase3/1 (MAPK3/1) in CT1 cells as determined by Western Blot analysis. By contrast, FGF2 did not affect MAPK3/1 phosphorylation status, but increased AKT phosphorylation status. Neither EGF nor IGF1 impacted AKT activity. Supplementation with a pharmacological inhibitor of MAPK3/1 (PD98059) prevented EGF-, IGF1-, and FGF2-dependent increases in CT1 cell proliferation. This inhibitor also completely abolished the increases in cell proliferation observed when all three factors were supplemented together. Supplementation with a pharmacological inhibitor of AKT (Wortmannin) reduced FGF2-stimulated CT1 proliferation, but did not impact EGF- and IGF1 effects. The AKT inhibitor partially attenuated the cooperative effects of all three factors on CT1 cell proliferation. A final study examined how the combination of EGF, FGF2, and IGF1 affect bovine embryo development. In vitro produced bovine blastocysts were cultured either with the combination of growth factors or vehicle only from day 8 to day 12 post-in vitro fertilization (IVF). The combination of EGF, FGF2, and IGF1 increased (P<0.05) the percentage of hatched blastocysts and outgrowth formation versus controls. Increased (P<0.05) diameters were detected in blastocysts treated with the combination of three growth factors on day 12 post-IVF when compared to controls. Treatment with the combination of EGF, FGF2, and also IGF1 increased (P<0.05) the change of diameter from day 8 to 12 post-IVF. In summary, these observations provide evidence that cooperative interactions of uterine-derived factors promote trophoblast proliferation and conceptus development in ways that may promote the establishment and maintenance of pregnancy in cattle. The mechanisms utilized for these activities remain unresolved, but MAPK3/1 and PI3K/AKT signaling systems appear to play integral roles in some of these processes.<br>Master of Science
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BREARD, EMMANUEL. "Regulation paracrine de la steroidogenese ovarienne par les interleukines 1 et 6." Caen, 1998. http://www.theses.fr/1998CAEN2028.
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Des etudes recentes ont montre que des facteurs paracrines non steroidiens, tels que les cytokines etaient susceptibles de jouer un role dans la regulation des fonctions ovariennes. Le but de cette etude a ete d'explorer les sites de synthese des interleukines 1 et 6 dans l'ovaire du lapin, et de determiner si ces cytokines pouvaient moduler la steroidogenese ovarienne, in vitro. A cette fin, le developpement de follicules preovulatoires multiples a ete induit chez le lapin par injections de gonadotropine equine, les ovaires ont ete ensuite excises et les cellules de granulosa et de theque, issus de follicules preovulatoires, ont ete isolees. Les deux types de cellule ont ensuite ete cultives 24 h, dans du milieu de culture additionne de serum de veau foetal, en presence ou en absence de gonadotropines. Les resultats montrent que les cellules de granulosa et de theque synthetisent des interleukines 1 et 6, et que cette production est inhibee par les gonadotropines fsh et hcg. Les interleukines 1 et 6, en contrepartie, inhibent la production de progesterone stimulee par les gonadotropines, dans les deux types cellulaires, et induisent une legere augmentation du nombre de cellules en culture. L'etude du mecanisme d'action de ces interleukines montre qu'elles affectent les etapes pre- et post-ampc du controle a long terme de la steroidogenese par les gonadotropines, et que ce mecanisme differe selon le type cellulaire considere. Une etude portant sur les cellules luteales bovines a egalement ete conduite. Elle montre que les interleukines 1 et 6 sont susceptibles de reguler la production de progesterone par les petites cellules luteales au cours d'incubations courtes, en presence ou en absence d'hcg. Cette regulation ne semble pas s'exercer par une modulation de la synthese d'une proteine mitochondriale impliquee dans le mecanisme de stimulation rapide de la steroidogenese. Nous concluons que les interleukines 1 et 6 sont des regulateurs potentiels des fonctions ovariennes ; qu'elles pourraient inhiber la differenciation des cellules de granulosa et de theque ; et que les gonadotropines, en inhibant la production des interleukines, s'opposent a l'action antigonadotropique de ces substances.
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VAIASICCA, SALVATORE. "Identification of the paracrine signals involved in immunomodulation, regeneration and cancer progression." Doctoral thesis, Università Politecnica delle Marche, 2020. http://hdl.handle.net/11566/274606.
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L’immunoterapia e la medicina rigenerativa coinvolgono l’uso di linee cellulari e loro derivati per il ripristino di funzioni compromesse. La comprensione della comunicazione cellulare (cross-talk) coinvolge numerosi segnali paracrine, i quali agiscono da modulatori dell’espressione genica delle cellule stesse. In particolare, le cellule staminali mesenchimali (MSC) sono promettenti candidati per la terapia cellulare, essendo dotate di proprietà specifiche (elevate proliferazione, capacità differenziativa, bassa immunogenicità e buone proprietà immune-soppressive e immune-modulatorie). In questo progetto di Dottorato, MSC derivate da Villi Coriali (hCV) e da Liquido Amniotico (hAF), da donne in buona salute, sono state caratterizzate ed è stato valutato l’effetto del terreno condizionato prelevato da esse in due linee di cellule del cancro ovarico. In particolare, gli esosomi all’ interno del terreno sono stati purificati e caratterizzati tramite microscopio e nanoparticle tracking. Sebbene le hCV-MSC sono risultate migliori in termini di proliferazione, il trattamento con hAF-MSC ha mostrato una riduzione di vitalità in modelli 2D, tuttavia, questi risultati non sono stati confermati in modelli 3D. Secondariamente è stato valutato l’effetto di un background patologico (Sindrome di Down) sulle caratteristiche delle hCV- MSC, riscontrando la maggior discrepanza in termini proliferativi, produzione di markers infiammatori e di radicali.
Infine, il terzo scopo è stato di valutare l’attività di inibizione della crescita cellulare in MCF-7 e PANC02, da parte di una combinazione tra due composti naturali Wasabia japonica e Active hexose correlated compound. La combinazione è stata testata tramite saggi di proliferazione, tossicità’ e azione immunomodulatoria, dimostrando che il mix presentava maggiori effetti di inibizione rispetto ai singoli composti.
In conclusione, gli studi sul cross-talk possono costituire un nuovo approccio per contrastare differenti condizioni patologiche ed intensificare l’azione del sistema immunitario.<br>Immunotherapy and regenerative medicine involves the use of living cells, or their derivatives, to modulate the function of endogenous cells. Cell communication, named “cross-talk”, involves numerous paracrine signals, exchanged between cells, which have been reported to modulate the behavior of specific cell lines. The Mesenchymal Stem Cells (MSC) are very promising candidate for cell-therapy due to their properties (high proliferation rate, differentiation capacity, low immunogenicity and good immuno-suppressive and modulatory properties). In this PhD project, Human Chorionic Villi (hCV) and Amniotic Fluid (hAF) derived from MSCs, have been characterized in terms of proliferative and differentiation abilities.
The first aim of this work was to study the interaction in two ovarian cancer cell lines, exposed to the conditioned medium of characterized hCV-MSCs and hAF- MSCs, focusing the attention in the soluble factors contained in the conditioned medium. The results derived from AF-MSCs showed a major effect on both ovarian cancer cells in 2D models but not replicated when using 3D cell cultures. As second aim, the interference of pathological backgrounds, i.e. Down Syndrome, on the hCV-MSCs abilities was investigated. The major discrepancies derived from the pathology were a reduction in term of proliferation an increase of production of inflammation markers and radical oxygen species.
Finally, the third aim was to evaluate the growth inhibitory activity of the combination between two natural compounds (Wasabia japonica and Active
hexose correlated), on MCF-7 and PANC02 cell lines. Our study demonstrated that the combination of these two natural compounds had a great inhibitory and anti-inflammatory activity compared to the single compounds on cancer cells.
Taken together our results, the cross-talk played the pivotal role in the regulation of cellular processes and its extremely variable effects, dependent on the considered cell line.
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Platel, Jean-Claude. "Activité calcique et communication paracrine avant synaptogenèse dans le développement du néocortex murin." Phd thesis, Université Joseph Fourier (Grenoble), 2005. http://tel.archives-ouvertes.fr/tel-00011566.
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Dans le néocortex murin, la division des cellules précurseurs a lieu dès le stade E11 et donne naissance aux premiers neurones pionniers dont les cellules de Cajal-Retzius. L'activité électrique spontanée, portée par les canaux ioniques, joue un rôle prépondérant dans le développement du système nerveux central. Comprendre la place des canaux ioniques et de la signalisation calcique dans les phases précoces de le neurogenèse était l'objectif principal de mon projet. Nous avons montré l'apparition précoce de canaux sodiques dépendants du voltage dans 55% des cellules neuronales à E13, dont les cellules de Cajal-Retzius. En parallèle, nous avons observé des activités calciques spontanées dans les cellules proliférantes et neuronales au même stade. La conception d'un logiciel d'imagerie nous a permis d'analyser statistiquement ces activités et d'identifier les canaux ioniques impliqués. Alors que les synapses ne sont pas encore formées, nous avons observé la mise en place d'activités synchrones au sein du néocortex et démontré l'existence de communications paracrines entre les cellules. De plus, nous avons identifié l'existence d'une cascade de signalisation où la dépolarisation des récepteurs glycinergiques active les canaux sodiques présents sur les neurones pionniers. Dans ces neurones, l'influx sodique entraîne une augmentation de calcium cytoplasmique via un échangeur Na+/Ca2+ puis une exocytose glutamatergique dont le libération paracrine induit l'activation d'autres cellules néocorticales. L'utilisation de la culture organotypique de cerveau nous a laissé entrevoir une implication physiologique majeure de cette cascade de signalisation dans la corticogenèse.
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Marttila, M. (Minna). "Paracrine and transcription factors mediating the natriuretic peptide gene expression during hemodynamic stress." Doctoral thesis, Oulun yliopisto, 1999. http://urn.fi/urn:isbn:951425449X.
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Abstract
Cardiac pathologies, including ventricular hypertrophy, are the primary cause of death in industrialized countries. Cardiac hypertrophy is often the consequence of work overload on the heart and characterizes several cardiovascular diseases, including atherosclerosis and hypertension. Cardiac hypertrophy is accompanied by genetic reprogramming characterized by the reexpression of several embryonic and growth response genes. Two of these genes encode A- and B-type natriuretic peptides (ANP and BNP), two cardiac-specific hormones secreted by myocytes, which play an important role in blood pressure regulation. The aim of the present study was to study the effect of acute pressure overload on BNP gene expression in the hearts of normal and hypertensive rats and then to examine the role of a passerine factor, angiotensin II (Ang II), on volume and pressure overload -induced ANP and BNP secretion and synthesis. Further, the aim was to characterize elements on the BNP promoter mediating hemodynamic stress in vivo.
BNP gene expression was studied in conscious spontaneously hypertensive (SHR) rats and together with ANP in two hypertensive, ream Transgenic rat models. The increased workload of the heart was produced by the infusion of vasopressin (AVP), phenylephrine (PHE) or bolus saline infusion. The increased workload caused rapid increases in cardiac BNP mRNA levels. Daring both AVP and PHE infusions, substantial increases in ventricular BNP mRNA levels were already evident after I h, and peak levels of BNP mRNA were reached at 4 h. Transgenic rats carrying one extra mouse renin gene showed impaired secretion and synthesis of ANP and BNP, while double transgenic rats carrying both human angiotensinogen and human renin genes showed augmentation of left atrial, but not ventricular BNP gene expression in response ta acute pressure overload. To characterize the elements mediating hemodynamic stress, bi-lateral nephrectomy was performed. GATA motif transduced the hemodynamic stress stimulus 26–28 hrs postnephrectomy in BNP gene expression.In conclusion, these results show that pressure overload abruptly stimulates the cardiac expression of a noncontractile protein gene BNP, suggesting that it may be used as a myocyte-specific marker of mechanical loading. BNP gene expression was augmented in atria hut nut in ventricles in response to pressure overload in an experimental model of hypertension, suggesting that high local levels of Ang II may differentially regulate cardiac gene expression in atrial and ventricular myocytes in double transgenic rats. At the transcriptional level, acute hemodynamic stress produced by nephrectomy increases BNP reporter expression through a GATA-dependent pathway.
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Greaves, Ralph Robert Sissak Handley. "Autocrine and paracrine factors in the control of gallbladder motility and gallstone pathogenesis." Thesis, Queen Mary, University of London, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.367583.
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Owino, Dorcas Vivian Apiyo. "Evaluation of role of paracrine/autocrine IGF-1 system in skeletal muscle adaptation." Thesis, University College London (University of London), 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.406510.
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Kimuli, Michael. "Reciprocal paracrine-mediated interactions between human urothelial and smooth muscle cells in-vitro." Thesis, University of York, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.428441.
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Jeffery, Victoria. "IL-6 and PGE2 regulate intestinal crypt homeostasis by autocrine and paracrine pathways." Thesis, University of East Anglia, 2017. https://ueaeprints.uea.ac.uk/66936/.
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The intestinal epithelium is the most rapidly renewing tissue in the body. Dynamic selfrenewal in the intestine is achieved through continuous proliferation of intestinal stem cells, and is under the tight regulation of numerous signalling pathways. IL-6 and PGE2 are pleiotropic cytokines, with well characterised roles in inflammation and intestinal tumorigenesis; however the roles for IL-6 and PGE2 in intestinal renewal during homeostasis remain unknown. The aim of this research was to determine the mechanisms through which autocrine and paracrine IL-6 and PGE2 regulate tissue renewal in the small intestine and colon, respectively, during homeostasis. This work also aimed to investigate a potential source of IL-6 and PGE2 in the intestinal lamina propria, the eosinophil. This thesis demonstrates that in the mouse small intestine, IL-6 signalling induces pSTAT3 activation in Paneth cells, which was shown to be the site of IL-6 receptor expression. This induced an increase in crypt cell proliferation and ISC expansion of small intestinal crypts, most likely through IL-6-classic signalling, with involvement of the WNT signalling pathway. The colonic epithelium expresses COX enzymes for PGE2 synthesis, and EP1-4 receptors for PGE2 signal transduction. Autocrine PGE2 signalling was required for colonic crypt cell proliferation during steady state renewal, which was mediated through the EP1/EP3 receptors. Paracrine signalling through the IL-6 and PGE2 pathways also induced small intestinal and colonic crypt proliferation respectively. A potential paracrine source of IL-6 and PGE, that resides in the intestinal lamina propria during health is the eosinophil. A novel spatial relationship between eosinophils and the stem cell niche (site of renewal) and crypt top (site of regeneration) was identified, suggesting that eosinophils play a role in modulating epithelial cell renewal during homeostasis. This work demonstrates that autocrine and paracrine IL-6 and PGE2 signalling is required for the maintenance of intestinal homeostasis.
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Keightley, Margaret Claire. "Autocrine and paracrine regulation of endothelial cell function by F-Prostanoid receptor signalling." Thesis, University of Edinburgh, 2010. http://hdl.handle.net/1842/4809.
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Endometrial adenocarcinoma, originating from the glandular epithelial cells of the uterine endometrial lining, is one of the most prevalent cancers amongst women in the Western world. The prostaglandin F2α (PGF2α) receptor (FP) is upregulated in endometrial adenocarcinoma. A previous microarray analysis of endometrial adenocarcinoma cells (Ishikawa) identified numerous targets of PGF2α-FP signalling including angiogenic factors, VEGF-A, FGF-2, CXCL1 and CXCL8 and antiangiogenic factors ADAMTS1. The regulation of VEGF-A, FGF-2, CXCL1 and CXCL8 was confirmed by previous studies using an in vitro model system, of Ishikawa cells stably expressing the FP receptor to levels observed in cancer (FPS cells). In this thesis, ADAMTS1 expression was found to be upregulated in endometrial adenocarcinoma samples compared to normal endometrium. Using FPS cells, ADAMTS1 expression was regulated in an extracellular signal regulated kinase 1/2 (ERK1/2) independent manner involving activation of nuclear factor of activated T cells (NFAT). Angiogenic and antiangiogenic proteins secreted by epithelial cells, in response to PGF2α-FP receptor signalling, could therefore regulate vascular function in a paracrine manner. Hence this thesis examines the role of angiogenic factors FGF2, CXCL1 and CXCL8, secreted into PGF2α-treated FPS cell conditioned medium (P CM), in the regulation of endothelial cell function in vitro. Firstly, using an in vitro model system, treatment of human umbilical vein endothelial cells (HUVECs) with P CM increased endothelial network formation and proliferation, compared to control CM. Immunoneutralisation of FGF2, CXCL1 and CXCL8 from the P CM reduced endothelial cell network formation and proliferation (P<0.05). In addition, inhibition of their receptors (FGFR1 and CXCR2) with chemical antagonists decreased endothelial cell network formation and proliferation (P<0.05) in response to treatment with P CM. This indicates that FGF2, CXCL1 and CXCL8 are paracrine effectors of FP-mediated endothelial cell network formation and proliferation. Next, the mechanisms by which FGF2 regulates P CM-induced endothelial cell network formation and proliferation were investigated. Using specific inhibitors of cell signalling, FGF2-FGFR1 was found to regulate endothelial cell proliferation via the mTOR pathway. In contrast, FGF2-FGFR1 signalling mediated endothelial cell network formation via the regulation of COX-2 expression and PGF2α synthesis in endothelial cells. Endometrial adenocarcinoma, originating from the glandular epithelial cells of the uterine endometrial lining, is one of the most prevalent cancers amongst women in the Western world. The prostaglandin F2α (PGF2α) receptor (FP) is upregulated in endometrial adenocarcinoma. A previous microarray analysis of endometrial adenocarcinoma cells (Ishikawa) identified numerous targets of PGF2α-FP signalling including angiogenic factors, VEGF-A, FGF-2, CXCL1 and CXCL8 and antiangiogenic factors ADAMTS1. The regulation of VEGF-A, FGF-2, CXCL1 and CXCL8 was confirmed by previous studies using an in vitro model system, of Ishikawa cells stably expressing the FP receptor to levels observed in cancer (FPS cells). In this thesis, ADAMTS1 expression was found to be upregulated in endometrial adenocarcinoma samples compared to normal endometrium. Using FPS cells, ADAMTS1 expression was regulated in an extracellular signal regulated kinase 1/2 (ERK1/2) independent manner involving activation of nuclear factor of activated T cells (NFAT). Angiogenic and antiangiogenic proteins secreted by epithelial cells, in response to PGF2α-FP receptor signalling, could therefore regulate vascular function in a paracrine manner. Hence this thesis examines the role of angiogenic factors FGF2, CXCL1 and CXCL8, secreted into PGF2α-treated FPS cell conditioned medium (P CM), in the regulation of endothelial cell function in vitro. Firstly, using an in vitro model system, treatment of human umbilical vein endothelial cells (HUVECs) with P CM increased endothelial network formation and proliferation, compared to control CM. Immunoneutralisation of FGF2, CXCL1 and CXCL8 from the P CM reduced endothelial cell network formation and proliferation (P<0.05). In addition, inhibition of their receptors (FGFR1 and CXCR2) with chemical antagonists decreased endothelial cell network formation and proliferation (P<0.05) in response to treatment with P CM. This indicates that FGF2, CXCL1 and CXCL8 are paracrine effectors of FP-mediated endothelial cell network formation and proliferation. Next, the mechanisms by which FGF2 regulates P CM-induced endothelial cell network formation and proliferation were investigated. Using specific inhibitors of cell signalling, FGF2-FGFR1 was found to regulate endothelial cell proliferation via the mTOR pathway. In contrast, FGF2-FGFR1 signalling mediated endothelial cell network formation via the regulation of COX-2 expression and PGF2α synthesis in endothelial cells. Angiogenesis is maintained by a balance of pro-and antiangiogenic factors. Hence, concomitantly with the upregulation of proangiogenic factors, antiangiogenic proteins ADAMTS1 and regulator of calcineurin 1 (RCAN1) were upregulated by P CM treatment of HUVECs. They were subsequently shown to limit endothelial cell network formation and proliferation in response to P CM. Finally, the role of PGF2α in angiogenesis was investigated using two in vivo models. PGF2α treatment did not increase angiogenesis in a sponge matrigel mouse model. In a xenograft mouse model, PGF2α-FP signalling increased expression of angiogenic factors in human epithelial cells and mouse stroma but this did not enhance microvessel density. Taken together, this thesis had highlighted that PGF2α-FP receptor signalling stimulates expression of pro-and antiangiogenic factors that in turn regulate endothelial cell function. However, in vivo studies demonstrate that PGF2α-FP receptor interaction does not impact on the level of angiogenesis but may control other aspects of vascular function.
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Bartlett, Johnathan Mark Seaverns. "Paracrine regulation of the rat testis : studies on seminiferous tubule-Leydig cell communication." Thesis, University of Edinburgh, 1985. http://hdl.handle.net/1842/19174.
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Zhou, Hong, and 周紅. "Novel aspects of autocrine/paracrine regulation of growth hormone secretion and synthesis in grass carp pituitary cells." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2003. http://hub.hku.hk/bib/B26392008.
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(Uncorrected OCR)
Abstract of thesis entitled
NOVEL ASPECTS OF AUTOCRINEIP ARACRINE REGULATION OF GROWTH HORMONE SECRETION AND SYNTHESIS IN GRASS CARP PITUITARY CELLS
Submitted by
ZHOUHONG
for the degree of Doctor of Philosophy at The University of Hong Kong
in March 2003
In this study, autocrine/paracrine regulation of growth hormone (GH) synthesis and secretion by local interactions of gonadotrophs and somatotrophs was examined in vitro in pituitary cells prepared from Chinese grass carp (Ctenopharyngodon idellus). Treatment with exogenous OH and gonadotropin (OTH) resulted in a dose-dependent increase in basal GH release, GH production, and GH mRNA levels. However, the opposite effects were observed by removing endogenous OR and OTH using immunoneutralization. Furthermore, GR and OTH immunoneutralizations at the pituitary level were effective in blocking the stimulatory influence on GH mRNA expression induced by GH-releasing factors in fish, including GnRH, dopamine, and PACAP38�Apparently" GH-induced GH gene expression was mediated by increasing the T1/2 ofGH mRNA in the cytoplasm and enhancing the production of GH primary transcripts in the nucleus. Since GH-induced OR mRNA gene expression could be blocked by inhibiting JAK2, P42144MAPK, P38MAPK, and PI3K, it is likely that the JAK/MAPK and JAK/PI3K pathways are involved in the GH receptor signaling. Similarly, exogenous GTH increased the production ofGH primary transcripts. However, it did not improve OR mRNA stability but rather enhanced the turnover of GH transcripts. GTR also increased cAMP production in carp pituitary cells. GTH-induced GH mRNA expression Was mimicked by activating cAMP synthesis and blocked by inhibiting adenylate cyclase (AC) and PKA.. GTH-induced OR mRNA expression was also sensitive to inhibition of JAKz, P42/44MAPK, P3SM.AP1C and PI3K. Similar inhibitions, except for PI3K, were all effective in blocking OR mRNA expression
induced by activation of cAMP synthesis. These results indicate that GTH may induce GR gene expression through the AC/ cAMP/PKA pathway secondary coupled to JAK.2 andlor MAPK. Apparently, a cAMP-independent PI3K component is also involved in the post-receptor signaling. Using a colunm perifusion approach, the dynamic interactions between somaotrophs and gonadotrophs were examined. In this case, exogenous OTR induced a rapid rise in basal GH secretion, whereas exogenous GR was found to inhibit basal GTR release. In parallel studies, GTHinduced OR mRNA expression was abolished by OR immunoneutralization. Similarly, GTR immunoneutralization blocked GR-induced OR mRNA expression in carp pituitary cells. These results, as a whole, indicate that endogenously secreted OH and GTR, besides their functions as endocrine hormones, serve as novel autocrine/paracrine factors at the pituitary level to modulate GH secretion, OH production, OH gene expression, and somatotroph sensitivity to stimulation by hypothalamic regulators. These stimulatory influences of GH and GTR on OR gene expression axe exerted at the level of GR rnRNA stability and OH gene transcription, presumably via a direct coupling to the JAK/MAPK and JAKiPI3K cascades or an indirect coupling via the AC/cAMP/PKA pathway. Apparently, a local il1trapituitary feedback loop is present. In this case, GTH released from gonadotrophs stimulates GH secretion in neighboring somatotrophs. GR release from somatotrophs is essential to maintain basal GH synthesis and secretion and also exerts a negative feedback on basal GTB release. This intrapituitary feedback loop formed by local interactions between gonadotrophs and somatotrophs may represent a novel mechanism to control OR gene expression in lower vertebrates.<br>abstract<br>toc<br>Zoology<br>Doctoral<br>Doctor of Philosophy
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日高, 京子, Kyoko Hidaka, 佳子 三輪, et al. "Paracrine factors of vascular endothelial cells facilitate cardiomyocyte differentiation of mouse embryonic stem cells." Elsevier, 2008. http://hdl.handle.net/2237/10608.
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Estévez, Cebrero María de los Ángeles. "Influence of paracrine signalling within the tumour microenvironment on progression in breast cancer models." Thesis, University of Nottingham, 2015. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.727116.
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Introduction: Cancer cells are affected by paracrine signalling from surrounding stromal cells. Here we investigate the role of kinases in this signalling using a model breast cancer (BC) co-culture system to identify novel paracrine signalling mechanisms supporting the growth and survival of tumour cells and potentially modulating epithelial to mesenchymal transition (EMT). Methods: The influence of paracrine signalling of the MSCs in the growth of luminal and basal-like breast cancer cells after the knock-down of human kinases, selected through a screen of a siRNA library, was investigated using a co-culture system that involves the culture of these transfected cells with or without human bone marrow-derived MSCs. An in silico analysis was also performed to investigate potential clinical relevance of these molecules. Results: The screen of the human kinase siRNA library in the MCF-7 cells co-cultured with MSCs revealed a number of kinases that seemed to be involved in the regulation of tumour growth. The knock-down of a subset, including GKAP1, CALM2, NEK7, MAPK7 and PI3KC2G, in the MCF-7, MDA-MB-231 and BT-549 cells growing alone or with MSCs resulted in the modulation of growth through autocrine or paracrine pathways and some may also be involved in the activation of the EMT pathways. Conclusion: There is a need for novel cancer biomarkers and targets to treat some forms of tumours such as the triple-negative BC, lacking a targeted therapy, or those that are resistant to the available ones. Here, the importance of the tumour microenvironment (TME) in the response to the inhibition of the targets in the cells was demonstrated. Potential therapeutic targets and pathways were presented as novel candidates for new treatments that need further investigation.
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Hirai, Shizuka. "Studies on the regulation of preadipocyte differentiation by paracrine factors secreted from muscle cells." Kyoto University, 2006. http://hdl.handle.net/2433/78167.
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Kyoto University (京都大学)<br>0048<br>新制・課程博士<br>博士(農学)<br>甲第12364号<br>農博第1545号<br>新制||農||924(附属図書館)<br>学位論文||H18||N4122(農学部図書室)<br>UT51-2006-J356<br>京都大学大学院農学研究科応用生物科学専攻<br>(主査)教授 矢野 秀雄, 教授 久米 新一, 教授 今井 裕<br>学位規則第4条第1項該当
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Grazzini, Eric. "Rôle endrocrine et paracrine de la vasopressine dans la physiologie de la glande surrénale." Montpellier 2, 1996. http://www.theses.fr/1996MON20058.
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La vasopressine (avp) est une neurohormone qui transmet des informations a travers l'organisme par l'intermediaire de recepteurs couples a des proteines g. L'avp regule la secretion de steroides de la glande surrenale des mammiferes. Au cours de cette etude, nous nous sommes interesses a la voie privilegiee (paracrine ou endocrine) par laquelle l'avp peut exercer ses effets sur la glande surrenale. Nous montrons que l'avp est secretee par la zone medullaire de la glande et que ces secretions ont la possibilite d'activer des recepteurs de sous-type v1a presents dans le cortex, ou des recepteurs de sous-type v1b presents dans la medulla. L'activation de ces deux sous-types de recepteurs induit une augmentation de la concentration en calcium intracellulaire a l'origine d'une secretion de catecholamines par la zone medullaire et d'une secretion de steroides par la zone corticale. L'existence au niveau des cellules du cortex de recepteurs a diverses hormones steroidogeniques nous a permis de montrer qu'il existe des regulations reciproques: ainsi, une stimulation par l'acth inhibe completement la reponse calcique induite par l'avp ou l'angiotensine ii
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Curley, Michael Kings. "Dissecting the paracrine interactions contributing to normal testicular function and during the ageing process." Thesis, University of Edinburgh, 2018. http://hdl.handle.net/1842/28972.
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The mammalian testis is divided into two distinct compartments which carry out its principal functions. Spermatogenesis occurs within the seminiferous tubules and androgen biosynthesis primarily occurs in the interstitial space. Both these processes are entirely dependent upon the two major testicular somatic cell populations - the Sertoli and Leydig cells respectively. In human males, testicular spermatogenic and endocrine function declines during the ageing process. Of particular significance is the reported age-related decrease in Leydig cell androgen production as androgens have been suggested to play a crucial role in supporting lifelong general health in men, with low circulating testosterone linked to an increased risk of developing chronic age-related cardiometabolic diseases. However, the relationship between ageing, testicular function and disease is not fully understood, impeding the development of novel therapeutic strategies to treat age-related testicular dysfunction. In one set of studies undertaken herein, a series of novel mouse models of premature ageing were utilised to begin to dissect the process of age-related testicular degeneration. Firstly, a novel knockout-first conditional allele of a previously reported premature-ageing model driven by Cisd2 (CDGSH Iron Sulphur Domain 2) deficiency was validated and the testicular phenotype characterised and compared to that of naturally aged mice at 18-months of age. Histological analyses revealed premature testicular atrophy at 6-months of age in CISD2 deficient mice, consistent with observations of the naturally aged testis. Circulating testosterone was significantly lower in CISD2-deficient mice compared to wild-type controls at 6-months of age and the luteinising hormone/testosterone ratio was significantly elevated, indicative of compensated Leydig cell failure. mRNA expression of key genes involved in androgen production were also significantly reduced in the CISD2-deficient testis, pointing to Leydig cell dysfunction in this model of premature aging. Next, Cre/LoxP technology was used to delete Cisd2 from specific testicular cell populations to determine which cell types control/support Leydig cell function during the ageing process. Testosterone production was unaffected when Cisd2 was disrupted in either the Leydig cell population or Sertoli cell population. These observations suggest that disruption to the testicular microenvironment in which Leydig cells reside, rather than intrinsic Leydig cell ageing, may play a significant role in age-associated Leydig cell dysfunction. A second set of studies were carried out to investigate the role of leukemia inhibitory factor (LIF) signalling in the maintenance of testicular function. LIF is a pleiotropic cytokine belonging to the interleukin-6 family. In the rodent testis, LIF is expressed in fetal life and adulthood; the peritubular myoid cells thought to be the main site of production. Given their anatomical location within the testis, LIF produced by peritubular myoid cells may act on both intratubular and interstitial cells to influence spermatogenesis and steroidogenesis respectively. Indeed, LIFR is expressed in germ cells, Sertoli cells, Leydig cells as well as testicular macrophages suggesting that LIF may be a key paracrine regulator of testicular function. However, the precise role of LIF/LIFR signalling in the testis is largely unknown. As such, models of testicular cell-specific Lifr deletion were generated using Cre/LoxP technology. Analysis of these novel models of conditional LIFR ablation revealed that LIFR is dispensable in germ cells for normal spermatogenesis. However, LIFR ablation from Sertoli cells resulted in a progressive degenerative phenotype, characterised by abnormal germ cell loss, sperm stasis, seminiferous tubule distention and subsequent atrophy of the seminiferous tubules. In a final set of studies, a rat model of Leydig cell ablation-regeneration was used to determine the regenerative capacity of human adipose-derived perivascular stem cells (hAd-PSC) as a potential therapy for testicular dysfunction. Following ethane dimethanesulphonate (EDS) mediated Leydig cell ablation, primary hAd-PSCs, cultured with or without LH, IGF-1, PDGFBB, T3 and ITS supplement, were transplanted into the rat testis and Leydig cell regeneration was monitored via serial measurements of circulating luteinising hormone (LH) and testosterone. Overall, hAd- PSCs had no impact on the recovery of circulating testosterone levels. However, when pre-cultured with the cocktail of hormone/growth factor supplements, the LH spike induced by the removal of testosterone negative feedback was dampened, suggesting the transplanted cells may promote Leydig cell regeneration. Whether these cells differentiate into Leydig cells, or simply provide paracrine support to the regenerating Leydig cells remains to be determined. Although Ad-PSCs may enhance regeneration kinetics, the transplanted cells were undetectable in the testis 5 weeks post transplantation suggesting they may not survive in the context of long term xenogeneic transplantation.
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Gonçalves, Bianca Mariani. "Impacto das vias intrapancreática, intravenosa e intra-capsular renal no transplante de células-tronco mesenquimais – regeneração morfofuncional do diabetes tipo I experimental." Botucatu, 2018. http://hdl.handle.net/11449/152810.
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Orientador: Luiz Henrique de Araújo Machado<br>Resumo: O diabetes mellitus (DM) é uma das doenças que mais tem aumentado sua incidência na última década. As células-tronco mesenquimais derivadas de tecido adiposo (CTMs-TA) possuem características imunomoduladoras e reparadoras, sendo capazes de reverter efeitos sistêmicos da doença. Sendo assim, nosso trabalho teve como objetivo avaliar o impacto do transplante de CTMs-TA pelas vias intravenosa, intrapancreática e intra-capsular renal em ratos diabéticos e comparar a que melhor exerce efeito regenerador. Para o estudo, utilizamos 45 ratos, wistar, fêmeas, divididos em 5 grupos: GCS – controle sadio; GCD – controle diabético; GIV – diabético, via intravenosa; GIP – diabético, via intrapancreática; GIR – diabético, via cápsula renal. Para a indução, utilizamos uma única aplicação intraperitoneal (i.p) de Aloxana (120mg/kg), e após 3 dias, os animais foram submetidos ao transplante com as CTMs-TA (2x106cel/animal). Após 15 dias do transplante, os animais foram eutanasiados. O transplante de CTMs-TA pela cápsula renal foi capaz de reverter a hiperglicemia, além de restaurar o diâmetro das ilhotas e restabelecer a função das massa β-pancreática. Concluímos que a cápsula renal foi a que apresentou melhores resultados na regeneração morfofuncional do pâncreas diabético. As CTMs-TA utilizadas neste estudo foram capazes de exercer um importante efeito parácrino, podendo ser utilizadas como alternativa para a melhoria da qualidade de vida de indivíduos diabéticos.<br>Mestre
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Miwa, Keiko, Jong-Kook Lee, Kyoko Hidaka, et al. "Paracrine Factors from Cultured Cardiac Cells Promote Differentiation of Embryonic Stem Cells into Cardiac Myocytes." Research Institute of Environmental Medicine, Nagoya University, 2003. http://hdl.handle.net/2237/7580.
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Ueda, Minoru, Fumitaka Kikkawa, Hideharu Hibi, et al. "Mesenchymal stromal cells of human umbilical cord Wharton's jelly accelerate wound healing by paracrine mechanisms." Thesis, Informa healthcare, 2012. http://hdl.handle.net/2237/18891.
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Kirn, Leonard Marcel [Verfasser]. "Tumor-stroma crosstalk in colorectal cancer: the role of paracrine hedgehog signaling / Leonard Marcel Kirn." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2019. http://d-nb.info/1202044972/34.
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Müller, Eike, Weijia Wang, Wenlian Qiao, et al. "Distinguishing autocrine and paracrine signals in hematopoietic stem cell culture using a biofunctional microcavity platform." Universitätsbibliothek Leipzig, 2016. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-208979.
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Homeostasis of hematopoietic stem cells (HSC) in the mammalian bone marrow stem cell niche is regulated by signals of the local microenvironment. Besides juxtacrine, endocrine and metabolic cues,
paracrine and autocrine signals are involved in controlling quiescence, proliferation and differentiation of HSC with strong implications on expansion and differentiation ex vivo as well as in vivo transplantation.
Towards this aim, a cell culture analysis on a polymer microcavity carrier platform was combined with a partial least square analysis of a mechanistic model of cell proliferation. We could demonstrate the discrimination of specific autocrine and paracrine signals from soluble factors as stimulating and inhibitory effectors in hematopoietic stem and progenitor cell culture. From that we hypothesize autocrine signals
to be predominantly involved in maintaining the quiescent state of HSC in single-cell niches and advocate our analysis platform as an unprecedented option for untangling convoluted signaling mechanisms in complex cell systems being it of juxtacrine, paracrine or autocrine origin.
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DARIMONT-NICOLAU, CHRISTIAN. "Controles hormonal et paracrine du developpement du tissu adipeux : de l'in vitro a l'in vivo." Nice, 1994. http://www.theses.fr/1994NICE4737.
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Le role modulateur de la triiodothyronine (t#3) sur l'effet mitogenique-adipogenique de la carba-prostacycline (cpgi#2), analogue stable de la prostacycline (pgi#2), a ete mis en evidence en utilisant les preadipocytes ob1771, cultives dans un milieu chimiquement defini. L'acide retinoique all-trans, dont le recepteur nucleaire possede une forte homologie de sequence avec celui de la t#3, est capable de mimer les effets modulateurs de t#3 sur la differenciation des cellules ob1771 ainsi que sur celle des precurseurs d'adipocytes de rat en culture primaire. Les effets de l'angiotensine ii (ang ii) sur la regulation de la production de pgi#2, chez les preadipocytes et les adipocytes, ont ensuite ete etudies in vitro et in vivo:? in vitro, l'ang ii, par l'intermediaire d'un recepteur de type at#2 present chez les adipocytes, controle l'effet adipogenique de pgi#2 selon un mode d'action paracrine. ? in vivo, la technique de microdialyse tissulaire a permis de montrer que la production de pgi#2, presente a l'etat basal dans le milieu extracellulaire du tissu adipeux periepididymaire de rat, est egalement stimulee par l'ang ii. Dans le cadre de l'implication eventuelle des prostaglandines (pgs) dans le controle de la balance differenciation-proliferation, une etude comparee de la production des pgs a ete entreprise in vitro sur des cultures de preadipocytes normaux (ob1771) ou transformes (ob17py), ainsi qu'in vivo sur le tissu adipeux periepididymaire et sur des fibrosarcomes, induits par injection de cellules ob17py, chez des souris athymiques. Pgi#2 apparait a la fois in vitro et in vivo comme un indicateur de la transformation preadipocytaire. L'ensemble de ce travail souligne l'importance de l'interaction des voies paracrines et endocrines dans le controle et la modulation de la differenciation adipocytaire induite par pgi#2
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Di, Lullo Elizabeth. "Pax6 and its paracrine activity in oligodendrocyte precursor cell migration in the developing neural tube." Paris 6, 2011. http://www.theses.fr/2011PA066737.
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Cette thèse s'intéresse au rôle du transfert de l'homéoprotéine Pax6 dans la migration cellulaire, en utilisant le tube neural de poulet comme modèle. Nous avons utilisé la technique de biotinylation de surface pour démontrer la présence extracellulaire de Pax6. Cette observation a soulevé la question de l'importance physiologique in vivo de ce pool extracellulaire de Pax6 (ePax6). L'identification de cellules positives pour Pax6 à proximité de pr'curseurs d'oligodendrocytes (OPCs) en migration nous a conduit à formuler l'hypothèse d'un rôle de ePax6 dans la migration des OPCs. Cette hypothse a été testée in vitro et in vivo via des expériences de gain ou perte de fonction. Suite à la neutralisation de ePax6, nous avons observé une diminution du nombre d'OPCs en migration, suggérant ainsi que ePax6 est activement impliqué dans la dispersion des OPCs. A l'inverse, lorsque la protéine Pax6 est ajoutée dans le milieu de culture d'une préparation de type open book du tube neural, la dispersion des OPCs est accentuée. Un effet similaire est observé suite à l'électroporation in ovo d'un plasmide codant pour une forme de Pax6 dotée d'un signal peptide. Nos résultats suggèrent une action non-autonome de Pax6 nécessitant son internalisation par les OPCs. Ainsi, nos expériences de perte de fonction ont pour effet de réduire la quantité de protéine transférée dans les cellules cibles. L'ensemble de nos observations mettent en évidence que le rôle des homéoprotéines ne se réduit pas à une simple activité transcriptionnelle mais consiste plutôt en un large panel de processus incluant ce qui est peut tre leur fonction la plus ancienne : assurer la communication cellulaire
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PINEAU, CHARLES. "Regulation paracrine de la fonction testiculaire chez le rat : etudes in vivo et in vitro." Rennes 1, 1990. http://www.theses.fr/1990REN10005.
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Ce travail a ete effectue in vivo et in vitro chez le rat a differents ages et par plusieurs approches experimentales. Nous demontrons principalement: 1) l'interet d'approches paralleles in vivo et in vitro pour l'etude des relations entre les cellules germinales et les cellules de sertoli; 2) l'existence d'une regulation des cellules de sertoli par les cellules germinales, celle-ci pouvant etre mediee par l'intermediaire d'un(de) facteur(s) diffusible(s); 3) que la regulation des cellules de sertoli par les cellules germinales depend du type de cellule germinale considere, de l'environnement hormonal, et qu'elle pourrait etre differente chez le mammifere impubere et adulte
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Kirn, Leonard [Verfasser]. "Tumor-stroma crosstalk in colorectal cancer: the role of paracrine hedgehog signaling / Leonard Marcel Kirn." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2019. http://d-nb.info/1202044972/34.
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Klein, Russell David. "The regulation of matrilysin expression in prostate carcinoma cells by paracrine interactions with stromal cells." Diss., The University of Arizona, 1999. http://hdl.handle.net/10150/288940.
Full textAbstract:
Matrilysin is a matrix metalloprotease that degrades extracellular matrix and basement membrane components. Matrilysin expression is elevated in prostate cancers and is associated with increased histological grade and clinical stage of prostate cancer. We have proposed that the overexpression of matrilysin in prostate cancer cells could be due to stimulation by paracrine factors from stromal cells. Human prostate cancer cell lines were cultured with prostate-derived fibroblasts and fibroblast conditioned media (PFCM). PFCM induced matrilysin expression in three of six prostate cancer cell lines, including the cell line LNCaP. Biochemical characterization of the matrilysin inducing activity in PFCM identified fibroblast growth factors (FGFs) as candidates for this activity. Recombinant FGF-1, FGF-2, FGF-9 and FGF-10 induced matrilysin expression in LNCaP cells. The expression of these FGFs by prostate fibroblasts was verified using RT-PCR. Using a specific inhibitor of FGF receptor activation, we demonstrated that a significant portion of the matrilysin inducing activity of PFCM is dependent on activation of LNCaP cell FGF receptors. Matrilysin expression in normal prostate epithelial cells (PrEC) is not enhanced by treatment with FGFs or PFCM. Aberrant expression of FGFR-1 was observed in LNCaP cells, revealing a potential explanation for the ability of FGFs to induce matrilysin in LNCaP but not PrEC cells. Matrilysin expression is also elevated in inflamed ductile and acinar prostate epithelial cells associated with infiltrating macrophages. Therefore, the ability of monocyte secreted factors to induce matrilysin expression in prostate epithelial cells was determined. Treatment of LNCaP and PrEC cells with conditioned media from activated monocyte cultures induced matrilysin expression in these cells. The factor responsible for this induction was identified as interleukin-1β (IL-1β) using an anti-IL-1β neutralizing antibody. IL-1β induced transactivation of a reporter construct containing cis-elements from the human matrilysin promoter in LNCaP cells, indicating an effect of IL-1β on matrilysin gene transcription. An inhibitor of NF k B activity, pyrollidine dithiocarbamate (PDTC), blocked induction of matrilysin in LNCaP cells by IL-1β. This result implies a role for NFκB in the induction of matrilysin expression by IL-1β, an implication supported by evidence that IL-1β induces NFκB activity in LNCaP cells.