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Thomson, Craig. "WNT5A in Malignant Peripheral Nerve Sheath Tumors." University of Cincinnati / OhioLINK, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1613742042185276.
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Allen, John C. "FGF4 Induced Wnt5a Gradient in the Limb Bud Mediates Mesenchymal Cell Directed Migration and Division." BYU ScholarsArchive, 2013. https://scholarsarchive.byu.edu/etd/4309.
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The AER has a vital role in directing embryonic limb development. Several models have been developed that attempt to explain how the AER directs limb development, but none of them are fully supported by existing data. I provide evidence that FGFs secreted from the AER induce a gradient of Wnt5a. I also demonstrate that limb mesenchyme grows toward increasing concentrations of Wnt5a. We hypothesize that the changing shape of the AER is critical for patterning the limb along the proximal to distal axis. To better understand the pathway through which Wnt5a elicits its effects, we have performed various genetic studies. We demonstrate that Wnt5a does not signal via the Wnt/β-catenin pathway. However, we show that Wnt5a mutants share many common defects with Vangl2 mutants suggesting that Wnt5a signals through the Wnt/planar cell polarity (PCP) pathway.
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Christman, Mark Andrew II. "WNT5A EXPRESSION IN HUMAN AND MURINE ATHEROSCLEROTIC LESIONS." Ohio University / OhioLINK, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1180659149.
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Bhatt, Pooja. "Understanding and Exploiting Wnt5a and GSK3 Signaling in Inflammatory Disease." Ohio University / OhioLINK, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1365012252.
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Bauer, Matthieu. "Biological functions and signaling cascades of novel isoforms of WNT5A." Paris 11, 2010. http://www.theses.fr/2010PA11T001.
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Jenty, Marion. "Rôle de la signalisation LRP1/Wnt5a dans le métabolisme du cholestérol." Thesis, Strasbourg, 2016. http://www.theses.fr/2016STRAJ025/document.
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L’athérosclérose débute par l’accumulation de cholestérol dans les cellules des parois artérielles, formant des plaques d’athéromes. LRP1 protège contre la maladie en inhibant l’accumulation intracellulaire de cholestérol et nous avions montré qu’une signalisation Wnt5a était impliquée dans cette inhibition. Le projet de thèse consistait à caractériser les mécanismes moléculaires de cette inhibition et à vérifier l’effet athéroprotecteur de Wnt5a. Nous avons montré in vitro et in vivo que Wnt5a inhibe l’accumulation de cholestérol via la stimulation de son export et l’inhibition de sa synthèse endogène. Nous avons ensuite observé que l’invalidation de Wnt5a spécifiquement dans les CMLv de souris LDLR-/- conduit à une augmentation des lésions athéromateuses après un régime riche en cholestérol, confirmant alors son rôle athéroprotecteur. Nos travaux ont ainsi permis de révéler le potentiel de Wnt5a en tant que cible thérapeutique dans le traitement contre l’athérosclérose<br>Protects against intracellular cholesterol accumulation and we identified the secreted protein Wnt5a as a partner of this inhibitory effect of LRP1. The aim of this thesis is to determine the molecular mechanisms by which the LRP1/Wnt5a signaling pathway prevents cholesterol accumulation in cells and to study the antiatherogenic potential of Wnt5a. We first showed in vitro and in vivo that Wnt5a decreases cellular cholesterol content by stimulating its efflux through the induction of cholesterol transporters expression and by down-regulating the expression of HMGCoA-reductase. Then we used mice deleted for Wnt5a specifically in smooth muscle cells, which present more atherosclerotic lesions than control mice after a high cholesterol diet. This confirms that Wnt5a protects against atherosclerosis and could be an interesting therapeutic target in the treatment of the disease
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Kummitha, China Malakondaiah. "Applied Molecular Recognition of HECA-452 and Wnt5a in Pathological Inflammation." Ohio University / OhioLINK, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1267990823.
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Susman, Michael Wen. "The Wnt5a-Ror Signaling Pathway in the Morphogenesis of the Embryo." Thesis, Harvard University, 2015. http://nrs.harvard.edu/urn-3:HUL.InstRepos:23845401.
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Embryonic development is orchestrated by relatively few conserved core developmental signaling pathways that are used reiteratively to grow, specify and shape all tissues in the body into their final functional forms. The Wnt5a signaling pathway is necessary to shape and extend various tissues during morphogenesis, but how Wnt5a signals within cells has long remained unclear and controversial. Through loss-of-function experiments in mice, we demonstrate that the Ror family of receptors mediates Wnt5a-dependent processes in vivo at multiple stages of embryonic development. Of previously proposed mediators of Wnt5a-Ror signaling, we identify Dishevelled phosphorylation, but not the inhibition of β-catenin-dependent transcription or the activation of the JNK pathway, as a physiological target of Wnt5a-Ror signaling. To further understand the molecular mechanisms underlying Wnt5a-Ror function, we performed a proteomic mass spectrometry screen to identify additional mediators of the Wnt5a-Ror pathway. This screen led to the discovery that Kif26b, an atypical and largely uncharacterized member of the kinesin superfamily, is part of an evolutionarily conserved signaling cassette with Wnt5a and Ror proteins during embryonic development. Interestingly, we found that Kif26b protein exhibits a polarized subcellular localization at the trailing edge of cultured mesenchymal cells and functions to promote the migration of these cells. Wnt5a triggers the degradation of Kif26b by a proteasome-dependent mechanism and negatively regulates cell migration in a Kif26b- dependent manner. Together, these findings identify a new noncanonical Wnt5a-Ror-Kif26b signaling pathway that links extracellular signaling to cytoskeletal changes that influences the movement, polarity and shape of developing tissues, and pathological situations where this signaling may be dysregulated.<br>Medical Sciences
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Pietilä, I. (Ilkka). "The role of Dkk1 and Wnt5a in mammalian kidney development and disease." Doctoral thesis, Oulun yliopisto, 2015. http://urn.fi/urn:isbn:9789526207216.
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Abstract This thesis focuses on mammalian kidney development and in particular on the question of how two Wnt signalling pathway genes, an antagonistic Dkk1 and an agonistic ligand Wnt5a, regulate the process. Wnts are secreted ligands that are involved in many developmental processes, including gonadal differentiation and kidney development, but also in various diseases and malformations. Wnts form a large signalling family containing 19 different glycoprotein ligands in mammals. Wnt signalling occurs via two different intracellular pathways. A canonical pathway proceeds via beta-catenin, and a non-canonical pathway utilizes other signalling molecules. Dkk1 is an antagonist of the canonical pathway and Wnt5a is considered a ligand that activates the non-canonical signalling pathway. As part of the thesis, I have studied the role of Dkk1 in kidney morphogenesis using a conditional mouse model, in which the gene is deleted in a cell specific manner from the collecting ducts. Dkk1 deficiency increased renal papilla growth and the risk of hydronephrosis. Research pointed out that the lack of Dkk1 in the collecting ducts increased cell proliferation and disturbed the balance of canonical Wnt signalling, which led to an overgrowth of renal papilla. This led to functional phenotypes including increased water reabsorption and changes in ion secretion/absorption. These changes are most likely due to altered Wnt7b signalling. The second part of the thesis examines the role of the non-canonical Wnt5a gene in kidney development with a conventional knock out mouse model. At the time work began on the thesis, no corresponding kidney phenotype had been published. The primary finding in kidneys lacking Wnt5a was an altered basement membrane organization of the collecting ducts and glomeruli. The phenotype is most likely the reason behind morphological phenotypes which vary from bilateral kidney agenesis to duplex collecting system. Notably, during the course of this study we found a mutation in the human WNT5A gene of a CAKUT patient. This is the first time Wnts have been shown to organize kidney development via basement membrane formation<br>Tiivistelmä Tämän väitöskirjan tarkoituksena on ollut tutkia munuaisen kehitystä ja kuinka kaksi Wnt-signalointireitin geeniä, signalointia estävä Dkk1 ja signalointia edistävä Wnt5a säätelevät sitä. Wnt ligandit ovat eritettäviä signaalimolekyylejä, jotka ovat osallisina monissa kehitysbiologissa prosesseissa kuten sukupuolen määräytymisessä ja munuaisen kehityksessä. Myös monissa taudeissa on havaittu muuntuneita Wnt geenien tuottotasoja. Wnt-geenit muodostava suuren signalointimolekyyliperheen, johon lukeutuu 19 jäsentä nisäkkäillä ja Wnt-signointi on jaettu perinteisesti kahteen signalointiryhmään. Dkk1 on kanonisen Wnt-signaloinnin estäjä ja Wnt5a:ta pidetään pääsaantiöisesti ei-kanonisena Wnt-ligandina. Väitöskirjassani olen tutkinut Dkk1 geenin toimintaa kohdennetussa Dkk1-poistogeenisessä hiiressä, jossa geenin toiminta on poistettu spesifisesti munuaisen kokoojaputkista. Dkk1:n puutos johtaa munuaisen papillan kasvuun ja lisää riskiä hydronefroksen muodostumiseen. Tutkimukset osoittivat että Dkk1:n puutos aiheuttaa lisääntynyttä solujakautumista kokoojaputkissa, jolloin Wnt-signaloinnin muutos aiheuttaa papillan ylikasvua. Ylikasvusta seuraa lisääntynyttä veden takaisin imeytymistä ja muutoksia ionien erittämisessä ja takaisin imeytymisessä. Todennäköisimmin muutokset johtuvat muuntuneesta Wnt7b signaloinnista, jota Dkk1 normaalisti säätelee. Väitöskirjan toisessa osassa tutkittiin ei-kanonisen reitin Wnt5a ligandin roolia munuaisen kehityksessä käyttäen poistogeenistä hiirimallia, jossa Wnt5a:n roolia munuaisenkehityksessä ei ollut julkaistu työn aloituksen aikaan. Wnt5a:n puutoksen havaittiin vaikuttavan tyvikalvon järjestymiseen kokoojaputkissa ja munuaiskeräsessä. Tyvikalvon häiriö on todennäköisin syy morfologisiin muutoksiin, jotka vaihtelevat molempien munuaisen puuttumisesta kaksois-kokoojatiehyen muodostumiseen. Työssä osoitetaan ensimmäistä kertaa kuinka Wnt-signalointireitin proteiinit säätelevät munuaisen kehitystä tyvikalvon muodostuksen kautta
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Low, Keri Lynn. "FGF4 and Wnt5a/PCP signaling promote limb outgrowth by polarizing limb mesenchyme /." Diss., CLICK HERE for online access, 2006. http://contentdm.lib.byu.edu/ETD/image/etd1612.pdf.
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Hosseini-Farahabadi, Sara. "Analysis of WNT5A function in development and disease using the chicken model." Thesis, University of British Columbia, 2014. http://hdl.handle.net/2429/46414.
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Mouse and human genetic data suggests that Wnt5a is required for jaw development but the specific role in facial skeletogenesis and morphogenesis is unknown. The aim of this thesis is to study functions of WNT5A during mandibular development in chicken embryos.
We initially determined that WNT5A is expressed in developing Meckel's cartilage but in mature cartilage expression was decreased to background. This pattern suggested that WNT5A is regulating chondrogenesis so to determine whether initiation, differentiation or maintenance of matrix was affected I used primary cultures of mandibular mesenchyme. I found that Wnt5a conditioned media allowed normal initiation and differentiation of cartilage but the matrix was subsequently lost. Collagen II and aggrecan, two matrix markers, were decreased in treated cultures. Degradation of matrix was due to the induction of metalloproteinases, MMP1, MMP13, and ADAMTS5 and was rescued by an MMP antagonist. The effects of Wnt5a on cartilage were mainly due to stimulation of the non-canonical JNK/PCP pathway as opposed to antagonism of the canonical Wnt pathway.
To increase the clinical relevance of my work I studied the functional consequences of two human WNT5A mutations (C182R and C83S) causing human Robinow syndrome. Retroviruses containing mutant and wild-type versions of WNT5A caused shortening of beaks and limbs; however, the phenotypes were more frequent and severe with mutations. Mechanisms responsible for micrognathia were assessed. Decreased cell proliferation and impaired chondrocyte organization and intercalation were seen with all constructs. The effects of mutant proteins on the migration of mesenchymal cells were tested in organ cultures of the mandible. The C83S and to a lesser extent C182R forms of WNT5A inhibited the normal migration of dye-labeled mesenchymal cells. The lack of cell migration was similar to that reported in Wnt5a null mice and therefore suggested that the WNT5A mutations are causing a loss-of-function.
We conclude that WNT5A is required during early chondrogenesis to block canonical signaling thereby allowing cartilage to form. In addition, WNT5A is required for cells to migrate within the mandible and perhaps to form the elongated shape of the lower jaw. Finally WNT5A in conditions of excess has detrimental effects on cartilage integrity.
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Daud, Tariq. "The role of WNT5a in airway remodelling in asthmatic airway epithelial repair." Thesis, University of Leicester, 2018. http://hdl.handle.net/2381/42778.
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Asthma is heterogeneous disease characterised by distinct tissue molecular phenotypes (Choy et al, 2015). However, the process of repair and remodelling remains ambiguous in this context. Although previous reports have shown elevated protein and mRNA expression of WNT5a, there is limited evidence in the literature to the major source of and function of WNT5a in asthma. Furthermore, WNT5a acting through the non-canonical axis exhibits functional cross talk with TGF-β1, which may influence repair and remodelling in asthma. We sought to evaluate protein expression of WNT5a and TGF-β1 in bronchial biopsies from a previously described cohort of subjects (9 healthy and 23 asthmatics) in whom aggregate gene signature profiles for Th2 and Th17 activity from tissue homogenates were available. After observing co-localised protein expression of both WNT5a and TGF-b1 in the epithelium, further investigations in BEAS-2B cells as a basal cell wound repair model were undertaken. We observed increased WNT5a protein expression pattern in vivo in asthma. WNT5a protein expression was significantly elevated in the epithelium in Th17 gene expression high asthmatic biopsies and the lamina propria, but not the airway smooth muscle bundle. We found a significant correlation and colocalisation of protein expression between TGF-β1 and WNT5a immunostaining in the epithelium suggestive of crosstalk. Further evidence supportive of cross talk was that both TGF-β1 and WNT5a were shown to induce SMAD2/3 nuclear translocation, which was inhibited by BOX-5 (a WNT5a inhibitor). Furthermore, WNT5a increased [Ca2+]I suggestive of noncanonical pathway engagement. Lastly, both WNT5a and TGF-β1 dual stimulation increased wound closure in BEAS-2B cells. Finally, stimulation of BEAS-2B cells with either TGF-β1 or WNT5a increased the expression of epithelial-mesenchymal transition (EMT) markers. WNT5a protein is increased in the airway epithelium in patients with asthma displaying a mucosal Th17-dependent gene signature. Additionally, we show potential in vitro evidence of TGF-β1-WNT5a cross talk via the SMAD2/3 axis, promoting EMT and epithelial wound closure. This study potentially highlights a novel crosstalk pathway between WNT5a-TGF-β1 as a possible epithelial repair mechanism employed in asthma that warrants further molecular and functional characterisation.
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Ripka, Stefanie. "Funktionelle Analyse des Glykoproteins WNT5A als Zielgen des Transkriptionsfaktors CUTL1 im Pankreaskarzinom." [S.l. : s.n.], 2007. http://nbn-resolving.de/urn:nbn:de:bsz:289-vts-59357.
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El, Asmar Zeina. "Rôle de Wnt5a dans l'homéostasie du cholestérol et deux pathologies l'athérosclérose et l'obésité." Strasbourg, 2011. http://www.theses.fr/2011STRA6201.
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Le déséquilibre de l’homéostasie cellulaire du cholestérol dans les macrophages et les CMLv ainsi qu’au niveau du tissu adipeux a plusieurs conséquences néfastes dans l’organisme vivant. Au niveau de la paroi vasculaire, le déséquilibre de l’homéostasie cellulaire du cholestérol induit également la formation des cellules spumeuses sécrétant un grand nombre de facteurs de croissance et de cytokines qui vont amplifier la réponse inflammatoire et contribuer ainsi au développement de la plaque d’ athérosclérose. De plus, dans le tissu adipeux, la modulation de l’homéostasie cellulaire du cholestérol favorise l’installation de l’obésité. La connaissance des molécules cibles et la compréhension des mécanismes impliqués dans la régulation de l’homéostasie cellulaire du cholestérol est donc primordiale pour prévenir l’accumulation intracellulaire du cholestérol et la formation des plaques d’athérosclérose. Le rôle de la protéine Wnt5a dans la régulation de l’accumulation cellulaire de cholestérol n’avait, à ce jour, pas été étudié. Nos résultats in vitro ont permis de montrer, pour la première fois, qu’en présence de LRP1, Wnt5a est exprimé et pourrait réduire l’accumulation cellulaire de cholestérol dans les MEFs après traitement avec un cocktail adipogénique. En plus, nous avons montré in vivo qu’en présence de LRP1, Wnt5a induit l’expression des gènes Sox9 et Cart1 marqueurs de la chondrogenèse et participe ainsi à l’activation de programme de la différenciation chondrocytaire au niveau des lésions athéroscléreuses. In vivo, nous avons montré que la surexpression de Wnt5a au dans le tissu adipeux blanc et brun chez la souris pourrait réduire l’accumulation du cholestérol dans les adipocytes. Nous avons montré que Wnt5a induit une diminution de l’expression des gènes codant pour les enzymes de la synthèse du cholestérol (HMGCoA synthase 2 et HMGCoA réductase) et pour le transporteur impliqué dans l’efflux du cholestérol (ABCA1) chez la souris<br>The imbalance of the cellular homeostasis of cholesterol in macrophages and VSMCs as well as adipose tissue has several adverse consequences in the organism. At the vessel wall, the imbalance of the cellular homeostasis of cholesterol induces the formation of foam cells secrete, many growth factors and cytokines. That amplifies the inflammatory response and contributes to the development of plate atherosclerosis. In adipose tissue, modulation of cellular homeostasis of cholesterol promotes the installation of obesity. Knowledge of target molecules and understanding of the mechanisms involved in regulating cellular homeostasis of cholesterol is essential to prevent the intracellular accumulation of cholesterol and the formation of atherosclerotic plaques. The role of Wnt5a protein in the regulation of cellular cholesterol accumulation had, to date, not been studied. In vitro, our results have shown for the first time we have shown in the presence of LRP1, Wnt5a is expressed and could reduce the cellular accumulation of cholesterol in MEFs after treatment with an adipogenic cocktail. In addition, we have shown in vivo in the presence of LRP1, Wnt5a induces the expression of genes Sox9 and Cart1 markers of chondrogenesis and thus contribute to the activation of chondrocyte differentiation program in terms of atherosclerotic lesions. In vivo, we showed that overexpression of Wnt5a in the white and brown adipose tissue in mice could reduce cholesterol accumulation in adipocytes. We demonstrated that Wnt5a induces a decrease the expression of genes encoding for enzymes involved in cholesterol synthesis (HMGCoA synthase and HMGCoA reductase 2) and the transporter involved in cholesterol efflux (ABCA1) in mice
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Seelamneni, Harsha. "Macrophage Polarization (M1/M2) and its Role in Wnt5a Secretion/Expression in Atherosclerosis." Ohio University / OhioLINK, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1357313250.
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Roarty, Kevin Patrick. "The role of TGF-ß and Wnt5a in mammary gland development and tumorigenesis." Thesis, Birmingham, Ala. : University of Alabama at Birmingham, 2008. https://www.mhsl.uab.edu/dt/2008p/roarty.pdf.
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Sowby, Whitney Herrod. "Determining the Role of Wnt5a Signaling in Embryonic Limb Outgrowth via Clonal Analysis." Diss., CLICK HERE for online access, 2008. http://contentdm.lib.byu.edu/ETD/image/etd2611.pdf.
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Awan, Sara. "Rôle de Wnt5a dans la fonction lysosomale, l’accumulation intracellulaire du cholestérol, et l’athérosclérose." Thesis, Strasbourg, 2019. http://www.theses.fr/2019STRAJ022.
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Nous avons identifié, un ligand de Wnt, Wnt5a, comme faisant partie intégrante du complexe mTORC1, qui régule la fonction lysosomal et favorise le trafic intracellulaire du cholestérol. En diminuant l’activité de mTORC1 et en activant l’axe autophagie-lysosome, Wnt5a adapte les concentration du cholestérol intracellualire aux besoins de la cellule. Wnt5a favorise l’export du cholestérol depuis les endosomal/lysosomal (LELs) vers le réticulum endoplasmique (RE), limite l’accumulation intracellulaire du cholestérol, et protège contre l’athérosclérose. D’un point de vue mécanistique, Wnt5a se lie aux membranes riches en cholestérol et interagit spécifiquement avec la protéine membranaire Niemann-Pick C1 (NPC1), la protéine soluble Niemann-Pick C2 (NPC2), deux protéines lysosomales qui régulent l’export du cholestérol à partir des LELs. En conséquence, l’absence de Wnt5a inhibe la fonction lysosomale et l’autophagie, ainsi que la sortie du cholesterol hors des LELs. Ceci resulte en l’accumulation de larges corps d’inclusion intracellulaires, de larges LELs riches en cholestérol, d’une diminution du cholestérol au niveau du RE<br>We identified the Wnt ligand, Wnt5a, as a member of the nutrient/energy/stress sensor, mTORC1 scaffolding complex, which drives lysosomal function and promotes cholesterol trafficking. By decreasing mTORC1 activity and by activating the autophagy-lysosomal axis, Wnt5a senses changes in dietary cholesterol supply, promotes endosomal/lysosomal (LELs) cholesterol egress to the endoplasmic reticulum (ER), and protects against atherosclerosis. Moreover, Wnt5a binds cholesterol-rich membranes and specifically interacts with two lysosomal proteins Niemann–Pick C1 and Niemann–Pick C2 that regulate cholesterol export from LELs. Consequently, absence of Wnt5a decoupled mTORC1 from variations in LELs sterol levels, and this resulted in accumulation of large intracellular inclusion bodies, large LELs and low ER cholesterol
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Borcherding, Nicholas. "Noncanonical Wnt signaling in breast cancer initiation and progression." Thesis, University of Iowa, 2014. https://ir.uiowa.edu/etd/1294.
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Schick, Diane. "Expression von Wnt5a - einem Mitglied der Wnt-Protein-Familie - in glatten Muskelzellen der Gefäßwand /." Inhaltsverzeichnis, 2004. http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&doc_number=013108307&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA.
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Soriano, Rodríguez Pilar. "WNT5A, SFRP5 y CRTC3: nuevas adipocinas relacionadas con la obesidad en la edad pediátrica." Doctoral thesis, Universitat de Girona, 2015. http://hdl.handle.net/10803/666754.
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WNT5A is a protein with proinflammatory properties recently related to insulin resistance. It is believed that this protein might be regulated by SFRP5, which sequesters WNT5A exerting its anti-inflammatory actions and preventing the onset of insulin resistance. Recently, it has been reported that both proteins can be secreted by the adipose tissue. CRTC3 is another protein expressed by the adipose tissue which plays important roles in energy metabolism. Recently, it has been reported that CRTC3 is associated with the development of obesity.
It is known that adipose tissue plays important roles in the regulation of energy homeostasis by secreting a number of molecules into the circulation. In this work, we will study the secretion of WNT5A, SFRP5 and CRTC3 by the adipose tissue in relation to obesity and cardiovascular risk markers in healthy children.
To this end, the study population consisted of 211 asymptomatic Caucasian children (103 boys and 108 girls) enrolled in a longitudinal study of cardiovascular risk factors. These children were recruited among those seen within a setting of preventive medicine. A longitudinal study was also performed in 130 children included in the cross-sectional study. All subjects underwent anthropometric and clinical examination and a blood sample was used to quantify the study parameters, including WNT5A, SFRP5 and CRTC3. We also obtained biopsies of visceral adipose tissue from 12 additionally children (10 boys and 2 girls) who underwent surgical procedures which were unrelated to the study. These biopsies were used ex vivo to study the secretion of WNT5A, SFRP5 and CRTC3 by the adipose tissue<br>La WNT5A es una proteína proinflamatoria relacionada recientemente con la resistencia a la insulina. Se cree que esta proteína podría estar regulada por la SFRP5, la cual secuestraría la WNT5A, ejerciendo así sus propiedades antiinflamatorias y evitando la aparición de la resistencia a la insulina. Recientemente se ha descrito que las dos proteínas pueden ser secretadas por el tejido adiposo de adultos. Por su parte, la proteína CRTC3 es expresada en el tejido adiposo donde juega un papel importante en el metabolismo energético. Recientemente, se ha descrito que el gen de la proteína CRTC3 está relacionado con el desarrollo de la obesidad metabólicamente complicada.
Se sabe que el tejido adiposo juega un papel importante en la regulación del equilibrio energético del organismo mediante la secreción de determinadas moléculas en la sangre. En este trabajo se estudiará la secreción de WNT5A, SFRP5 y CRTC3 por parte del tejido adiposo y su relación con la obesidad y marcadores de riesgo cardiovascular en la edad pediátrica.
Para tal fin, se ha diseñado un estudio transversal con una muestra de niños sanos de 7 años de edad (n = 211; 103 niños y 108 niñas), no seleccionados, provenientes de la población general, reclutados en los centros de atención primaria, y un estudio longitudinal con 130 niños (63 niños y 67 niñas), estudiados a los 3 años de su inclusión en el estudio inicial. A todos ellos se les realizó un examen clínico y antropométrico. Se obtuvo una muestra de sangre que se utilizó para realizar una analítica general y cuantificar los marcadores en estudio, que incluyen: WNT5A, SFRP5 y CRTC3. Adicionalmente, se obtuvieron biopsias de tejido adiposo visceral de 12 niños (10 niños y 2 niñas) que se sometieron a una intervención quirúrgica programada por causas externas al estudio. Este tejido adiposo se utilizó en estudios ex vivo para estudiar la secreción de las proteínas WNT5A, SFRP5 y CRTC3.
Los resultados obtenidos demuestran que las proteínas WNT5A, SFRP5 y CRTC3 son secretadas por el tejido adiposo y en mayor cantidad por el tejido adiposo visceral en niños prepuberales sanos. Además, concentraciones bajas de SFRP5 y altas de WNT5A y CRTC3 se relacionan con un perfil metabólico más desfavorable, consistente en una relativa disminución de la adiponectina en sangre, aumento de la resistencia a la insulina y aumento del índice de masa corporal.
El estudio del eje WNT5A - SFRP5 ha demostrado que las dos proteínas se relacionan positivamente tanto en el medio condicionado de las biopsias de tejido adiposo como en el suero de los niños sanos. Además, nuestros resultados demuestran que las concentraciones bajas de SFRP5 en sangre potencian la relación entre WNT5A y el aumento de la resistencia a la insulina y de parámetros de función hepática.
Estos resultados aportan evidencias del importante papel del tejido adiposo en la secreción de las proteínas WNT5A, SFRP5 y CRTC3 y su relación con marcadores conocidos de riesgo metabólico y el desarrollo de alteraciones metabólicas en etapas precoces de la vida
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Donandt, Susanne [Verfasser]. "Charakterisierung der funktionellen Rolle von Wnt5a in Keratinozyten bei der Psoriasis vulgaris / Susanne Donandt." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2009. http://d-nb.info/1023784653/34.
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Yang, Tian. "A prickly situation: Prickle1 function depends on the signaling context." Diss., University of Iowa, 2013. https://ir.uiowa.edu/etd/1517.
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The gene PRICKLE1 is important for human brain function, as mutations in PRCKLE1 are associated with progressive myoclonus epilepsy (PME). Mutations in prickle orthologs could cause seizures in flies, zebrafish and mice, suggesting a conserved role of Prickle protein in seizure from fruit flies to humans. The underlying molecular mechanism how PRICKLE1 mutation causes PME is still unknown.
Prickle1 is part of the planar cell polarity (PCP) pathway, which regulates cell polarity within plane of cell sheets. In Drosophila, prickle is recruited to one side of the cell by another PCP protein, Van Gogh. This asymmetric protein localization of Van Gogh/prickle establishes cell polarity. In zebrafish and Xenopus, loss of Prickle or Van Gogh like (Vangl) genes causes PCP phenotypes, which seemingly supports the Prickle/Vangl protein interaction and the role of Prickle in PCP pathway.
The function of Prickle in mammals has not been analyzed. It is possible that mammalian Prickle also interacts with Vangl to mediate PCP signaling based on the conserved role of prickle from Drosophila to Xenopus. If Prickle1 interacts with Vangl and regulate PCP pathway, the PME we observed in humans might be associated with loss of neuronal polarity and impaired neuron activity. Therefore, to understand whether Prickle1 mediates Vangl signaling in mammals could be a step toward revealing the etiology of PME in human patients.
Therefore, I analyzed the function of Prickle1 in three developmental processes, the limb development, the palate development, and the caudal migration of facial branchimotor neurons (FBMs), in which the function of PCP pathway, especially Vangl2, has been described. Supporting the interaction between Prickle1 and Vangl, mutations in either Prickle1 or Vangl2 leads to shorter limbs. However, Prickle1 and Vangl2 only have limited overlap in mRNA expression in the digit tips. This raises the question as to how impaired Prickle1/Vangl2 protein interaction in these cells in the digit tips cause defective growth of the whole limb. It also suggests alternate function of Prickle1 other than mediating Vangl2 function.
This interaction between Prickle1 and Vangl2 is further challenged by the limited function of Vangl but the essential role of Prickle1 in palate development, which suggests that the function of Prickle1 is independent of Vangl2.
In the caudal migration of FBMs, Prickle1 mutation impairs this migration process dose-dependently. This is different from Vangl2 mutation, which completely blocks the caudal migration and partially impairs the lateral migration of FBMs. More importantly, Prickle1 is expressed by the neurons, while Vangl2 functions in the surrounding cells, which again raises the question as to whether and how the two proteins could interact if they are not expressed in the same cell.
These results together question the model that Prickle1 is the intracellular partner of Vangl2, but support Prickle1 function might be independent of Vangl. Actually, it is possible that Prickle1 is part of gene expression regulation machinery: Prickle1 mutation affects Wnt5a expression in the limb and Shh expression in the palate. Although this regulation mechanism is still unknown, it suggests that defective gene expression might be related to PME caused by PRICKLE1 mutation.
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Badiglian, Filho Levon [UNIFESP]. "Análise imuno-histoquímica da via WNT em neoplasias epiteliais ovarianas e ovários normais." Universidade Federal de São Paulo (UNIFESP), 2009. http://repositorio.unifesp.br/handle/11600/8936.
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Publico-094.pdf: 903461 bytes, checksum: edf5b6e40862ad70fc99b723417b0669 (MD5)<br>Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)<br>Objetivo: Analisar as vias canônica e não-canônicas da família Wnt no ovário normal e na neoplasia benigna e maligna do ovário. Métodos: Obtiveram-se tecidos ovarianos no período entre 1993 e 2004. As pacientes foram divididas em três grupos: Grupo A, neoplasia ovariana epitelial maligna (N = 38); Grupo B, neoplasia ovariana epitelial benigna (N = 28) e Grupo C, ovários normais (N = 26). A imunoexpressão para Wnt1, Frizzled-1 (FZD1), Wnt5a, Frizzled-5 (FZD5) e Betacatenina foi avaliada em cada grupo. Resultados: A proporção de pacientes Wnt1-positivas no grupo A (29,4%) foi significantemente maior do que nos grupos B (4,3%) e C (9,1%) (p = 0,020). A proporção de mulheres FZD1-positivas no grupo C (54,5%) foi significantemente menor do que nos grupos A (97,1%) e B (90,0%) (p < 0,001). A proporção de pacientes wnt5apositivas foi significantemente maior no grupo A (80,0%) comparado aos grupos B (25,0%) e C (27,3%) (p<0,001). A proporção de pacientes Beta-catenina-positivas no grupo C (95,8%) foi significantemente maior do que no grupo B (52,4%) (p = 0,004). A comparação nas curvas de sobrevida no grupo A relacionada à expressão de Wnt5a mostrou diferença significante entre as pacientes positivas e negativas, sendo que as pacientes Wnt5a-positivas apresentaram resultados piores (p=0,050). Conclusão: Os achados demonstram que as vias relacionadas ao Wnt5a têm papel relevante na neoplasia ovariana maligna. Outrossim, a imunoexpressão do Wnt5a revelou ser marcador de mau prognóstico para câncer de ovário.<br>Objectives: To analize the canonical and noncanonical Wnt pathway in normal ovary, benign ovarian tumor and ovarian cancer. Methods: Ovarian specimens were obtained from surgeries performed between 1993 and 2004. The patients were divided in three groups: Group A, epithelial ovarian cancer (N = 38); Group B, benign epithelial neoplasia (N = 27) and Group C, normal ovaries (N = 26). Immunoreactivity for Wnt1, FZD1, Wnt5a, FZD5 and -catenin was scored for each group. Results: The proportion of Wnt1 positive women at the group A (29.4%) was significantly higher than the group B (4.3%) and C (9.1%) (p = 0.020). The proportion of FZD1 positive patients in group C (54.5%) was significantly lower than the group A (97.1%) and B (90.0%) (p < 0.001). The proportion of Wnt5a positive women was significantly higher for group A (80.0%) compared to the group B (25.0%) and C (27.3%) (p<0.001). The proportion of ß-catenin positive patients in the group C (95.8%) was significantly higher than the group B (52.4%) (p = 0.004). Comparison of the survival curves in group A according to Wnt5a expression showed a significant difference between positive and negative patients, whereas the Wnt5a positive women showed worse results (p=0.050). Conclusion: Our findings suggest that the pathways related to Wnt5a have an important role in ovarian malignant neoplasia. Furthermore, Wnt5a was found to be a predictor of poor prognosis for ovarian cancer.<br>FAPESP: 06/51401-1<br>TEDE<br>BV UNIFESP: Teses e dissertações
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Vale, Duarte Pereira Claudia Patricia. "Inflammatory Wnt5A signaling in macrophages as novel target for anti-inflammatory action of activated protein C /." [S.l.] : [s.n.], 2009. http://opac.nebis.ch/cgi-bin/showAbstract.pl?sys=000278496.
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Wallkamm, Veronika [Verfasser], and D. [Akademischer Betreuer] Wedlich. "Unterschiede und Gemeinsamkeiten der nicht-kanonischen Wnt-Liganden Wnt5a und Wnt11 / Veronika Wallkamm. Betreuer: D. Wedlich." Karlsruhe : KIT-Bibliothek, 2014. http://d-nb.info/1059803143/34.
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Dahl, Tiffanie M. "Role of Wnt5a and Possible Pathway of Action Through Ror2 in Proximodistal Outgrowth of the Limb." BYU ScholarsArchive, 2011. https://scholarsarchive.byu.edu/etd/2600.
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Despite over 60 years of study, the molecular pathways and mechanisms governing limb outgrowth and patterning remain poorly understood. Fgfs expressed in the AER are known to be necessary and sufficient for proximodistal limb outgrowth and have been proposed to have a chemoattractive role. Wnt5a is a secreted factor which is expressed in a gradient in the distal limb with the highest concentration next to the AER. The presence of the AER is necessary to establish this gradient. Expression of Wnt5a in a concentration dependant manner can be induced in the limb through the implantation of a bead soaked in recombinant Fgf4 protein. This indicates that Fgfs from the AER may establish the gradient of Wnt5a in the limb mesenchyme. Wnt5a-/- mutants exhibit severe shortening of the face, limbs, and body axis, with limbs being progressively truncated proximally to distally. In normal limb proximodistal outgrowth, cells are seen to grow directionally toward the AER. Previous studies done in the Barrow lab, as well as those done by myself, have shown that if a portion of the AER is removed and the cells proximal to this area are labeled, those which are close enough to intact AER will redirect their growth toward this intact AER. When Wnt5a secreting cells are implanted in the limb mesenchyme of the chick this ectopic source of Wnt5a is sufficient to redirect the growth of the mesenchyme cells toward the Wnt5a source. This indicates that the AER may mediate directed growth of limb mesenchyme cells through the establishment of the Wnt5a gradient which provides positional information to the cells. This Wnt5a gradient results in the recruitment of the mesenchyme cells toward the AER. The Ror2 receptor has been found to be involved in several different pathways involving Wnt5a which are involved in changes in polarity and migration. This makes Ror2 a likely candidate for causing changes in cell polarity and migration during distal outgrowth in the limb. To test whether Ror2 is necessary for the polarizing response of limb mesenchyme cells to the Wnt5a gradient in vivo I co-transfected a dominant-negative Ror2 (Ror2ΔC) and a GFP expression vector in the embryonic chick limb using sonoporation. Limb mesenchyme cells transfected with dominant-negative Ror2 grew as radial clones in contrast to the directional outgrowth of the control limb mesenchyme cells along the proximodistal axis. This indicates that cells expressing the dominant-negative Ror2 could no longer respond to the Wnt5a gradient in the limb mesenchyme. This supports a role for Ror2 as a receptor or co-receptor for Wnt5a in mediating directional growth and movement during proximodistal outgrowth and patterning in the limb.
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Ujita, Mari. "Impaired Wnt5a signaling in extravillous trophoblasts: Relevance to poor placentation in early gestation and subsequent preeclampsia." Kyoto University, 2019. http://hdl.handle.net/2433/242904.
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Skeyni, Alaa. "Mechanisms of atherosclerotic lesion formation via Wnt5a signaling and its impact on vascular cognitive impairment (VCI)." Electronic Thesis or Diss., Strasbourg, 2024. http://www.theses.fr/2024STRAJ049.
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Partie 1 : Le trafic lysosomal est lié à la détection du cholestérol, jouant un rôle central dans le métabolisme cellulaire et les maladies cardiovasculaires. Nos travaux montrent que Wnt5a est un inhibiteur de PIKfyve et régule les mouvements lysosomaux critiques pour l’homéostasie du cholestérol. La perte de Wnt5a active store-operated calcium entry (SOCE) via Orai1/STIM1, stimule CDK5/p25 et augmente l’activité de PIKfyve, entraînant l’accumulation périnucléaire des lysosomes. Cela empêche la détection du cholestérol par mTORC1. La LAL est dégradée via Endoplasmic reticulum-associated protein degradation (ERAD), provoquant l’accumulation d’esters de cholestérol et activant la biosynthèse endogène. Wnt5a contrôle ainsi le trafic lysosomal, protégeant contre l’accumulation de cholestérol et les maladies cardiovasculaires. Partie 2 : L’insuffisance cognitive vasculaire (ICV) découle des maladies cérébrovasculaires. Chez des souris smLRP1- (modèle d’athérosclérose) nourries au cholestérol, les tests NORT et labyrinthe en Y montrent des déficits de mémoire à long terme (0.54 vs 0.64 ; p=0.0001) et à court terme (58.3 % vs 65.6 % ; p=0.015). L'analyse morphométrie basée sur les voxels (VBM) révèle des changements dans les cortex périrhinal/entorhinal, hippocampe (gyrus dentelé/CA1), striatum et amygdale. L’imagerie par tenseur de diffusion (ITD) montre une augmentation d’anisotropie fractionnaire et une réduction de diffusivité radiale, diffusivité moyenne et diffusivité axiale, indiquant des altérations microstructurales dans la matière grise. L’IRM fonctionnelle révèle une hyperconnectivité entre le cortex entorhinal et le réseau par défaut. Nos résultats montrent pour la première fois que l’athérosclérose peut causer une pathologie ressemblant à l’ICV et des déficits mnésiques chez la souris<br>Lysosomal trafficking is linked to cholesterol sensing, playing a key role in cellular metabolism and cardiovascular disease. Our work shows that Wnt5a inhibits PIKfyve and regulates lysosomal movements critical for cholesterol homeostasis. Loss of Wnt5a activates SOCE via Orai1/STIM1, stimulates CDK5/p35/p25, and increases PIKfyve activity, leading to lysosomal perinuclear clustering. This prevents cholesterol sensing by mTORC1. LAL is degraded via ERAD, causing cholesteryl ester accumulation and activating cholesterol biosynthesis. Wnt5a thus regulates lysosomal trafficking, protecting against cholesterol accumulation and cardiovascular diseases. Vascular Cognitive Impairment (VCI) is derived from cerebrovascular disease. In smLRP1- mice (a model of atherosclerosis) fed cholesterol, NORT, and Y-maze tests revealed long-term memory deficits (0.54 vs 0.64; p=0.0001) and short-term memory impairments (58.3% vs. 65.6%; p=0.015). VBM analysis showed changes in the perirhinal/entorhinal cortices, hippocampus (DG/CA1), striatum, and amygdala. Diffusion tensor imaging (DT-MRI) analysis revealed an increased fractional anisotropy and reduced radial diffusivity, mean diffusivity, and axial diffusivity, suggesting microstructural changes. Resting-state fMRI revealed hyperconnectivity between the entorhinal cortex and the default mode network. For the first time, we show that atherosclerosis can cause VCI-like pathology manifested by memory deficits in mice
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Nai, Laura LN. "Ruolo della via di segnale di Wnt5a nel fenotipo dei miofibroblasti sub-epiteliali intestinali in corso di Colite Ulcerosa." Doctoral thesis, Università degli studi di Padova, 2011. http://hdl.handle.net/11577/3421990.
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ABSTRACT
Background: Wnts are a highly conserved family of secreted glicoproteins involved in several physiological and pathological processes. Intestinal subepithelial myofibroblasts (ISEMFs), a cellular population releasing growth factors and cytokines involved in tissue remodelling, have been recently identified as a source of Wnts ligands. Since Wnt5a, the main ligand of the non-canonical pathway, plays a pivotal role in intestinal epithelial repair and is up-regulated in chronic inflammatory disorders such as rheumatoid arthritis, the aim of our study was to evaluate, in ISEMFs derived from normal subjects and ulcerative colitis (UC) patients, the expression of Wnt5a and its receptors and determine its autocrine role on ISEMFs. Methods: ISEMFs were isolated from colonic mucosa of healthy subjects (n=6) or from patients with UC (n=10). Wnt5a and Frzd1, 2, 4, 5 expressions was evaluated by quantitative RT-Time PCR and Western Blot. To determine the autocrine effect of Wnt5a, we performed functional studies using Wnt5a KO by shRNA or exposing ISEMFs to human recombinant Wnt5a. Following 96 hours culture, cell proliferation was quantitated by 3H-tymidine incorporation and cell cycle analysis. To evaluate anti-apoptotic role of Wnt5a, we performed functional studies exposing ISEMFs to human recombinant Wnt5a and staurosporin. Following 24 hours culture Annexin V and caspase-3 assay was estimated. To identify pathway induced by Wnt5a signal, functional studies using β-catenin KO by shRNA or exposing ISEMFs to Ca2+ inhibitors was performed and CamKII protein levels was measured by Western blot. Results: UC-derived ISEMFs showed a significantly higher Wnt5a expression at mRNA and protein level (p<0.05) in basal condition as compared to controls. Furthermore, as compared to controls UC-derived ISEMFs produced significantly higher amounts of Wnt5a following exposure to LPS or TGFβ (p<0.05). ISEMFs derived both normal and UC patients showed a similar pattern of Wnts receptors. Wnt5a silencing in UC-derived ISEMFs and in control ISEMFs, caused a significant reduction in cell proliferation (p<0.05). Indeed, rWnt5a supplementation stimulated cell proliferation and resistance to staurosporin induced-apoptosis. Wnt5a signal is β-catenin independent because supplementation of rWnt5a in KO β-catenin ISEMFs led to a significative increase of cell proliferation (p<0.05). On the contrary,Wnt5a signal seems to be mediated by CamKII, promoting an increase of its phosphorilation. Conclusions: ISEMFs from UC patients produce an excess of Wnt5a that is able to stimulate cellular proliferation, resistance to apoptosis and that acts by CamKII activation. We speculate that Wnt5a plays a key role to expand the ISEMFs population in UC patients and might contribute to tissue damage and remodeling during chronic inflammation.<br>Wnt5a rappresenta il ligando prototipo della via non canonica di Wnt, via di segnale coinvolta nei processi di embriogenesi, riparazione tissutale e carcinogenesi dell’epitelio intestinale. Fisiologicamente, Wnt5a agisce sulla migrazione e proliferazione di tipi cellulari diversi coinvolti nel mantenimento dell’omeostasi epiteliale, fungendo da mediatore nel dialogo tra epitelio e mesenchima. Numerosi dati sperimentali suggeriscono inoltre che l’aumento di Wnt5a possa essere un meccanismo comune dell’infiammazione cronica in quanto è sovra-espresso nell’artrite reumatoide, nell’aterosclerosi e nella psoriasi. Abbiamo pertanto iniziato ad esaminare il ruolo di Wnt5a nell’infiammazione cronica intestinale.
Il modello preso in esame è rappresentato da miofibroblasti subepiteliali intestinali (ISEMFs) da Rettocolite Ulcerosa (RCU). Le ISEMFs sono cellule coinvolte nell’omeostasi intestinale: nell’intestino rappresentato il maggior sito di produzione del collagene e di altre proteine della matrice extracellulare, promuovendo dunque il rimodellamento tessutale. Inoltre interagiscono con le cellule epiteliali, le staminali e i macrofagi promuovendo e la restituzione epiteliale e la secrezione di citochine e chemochine. Si è osservato che nella mucosa dei pazienti affetti da IBD, il numero di queste cellule è significativamente aumentato rispetto a quello della mucosa sana, e che un’alterazione della loro funzionalità è coinvolto nella fisiopatologia delle IBD.
L’aumentata espressione di Wnt5a a livello trascrizionale e proteico è stata verificata in soggetti affetti da RCU, con correlazione diretta con il grado di attività di malattia. Studi di immunoistochimica hanno permesso, mediante co-localizzazione con α-SMA, di osservare la distribuzione di Wnt5a nel tessuto e la sua preponderante espressione in miofibroblasti sub epiteliali. La caratterizzazione di Wnt5a è stata dunque effettuata su miofibroblasti primari estratti da mucosa di Rettocolite Ulcerosa e tessuto controllo. Cellule derivate da tessuto infiammato hanno mostrato maggiori livelli di espressione proteica di Wnt5a. Dosaggi del trascritto e western blotting hanno permesso di osservare che il TGFβ e LPS sono in grado promuovere una sovra-espressione di Wnt5a nei miofibroblasti intestinali. Abbiamo quindi condotto dei saggi per verificare se Wnt5a regolasse caratteristiche fisiologiche e fenotipiche nelle ISEMFs stesse. A tal fine,dopo aver verificato la presenza dei recettori per Wnt5a, abbiamo iniziato degli studi di tipo funzionale mediante RNA interference (RNAi) per lo spegnimento genico (loss of function); perciò abbiamo messo a punto la metodica per il Knockdown di Wnt5a in colture primarie di ISEMFs con vettori adenovirali codificanti shRNA. Viceversa sono stati condotti degli studi di gain of function supplementando al terreno di coltura cellulare la proteina purificata rWnt5a. Sono stati effettuati dei saggi proliferazione rilevata mediante il metodo dell’incorporazione della timidina triziata da cui emerso che nelle ISEMFs Wnt5a promuove la proliferazione. Inoltre sono stati effettuati dei saggi sul ciclo cellulare mediante colorazione di ioduro di propidio e di resistenza all’apoptosi mediante anessina V e test di attivazione della caspasi-3, da cui emerge che questa glicoproteina promuove la sopravvivenza cellulare.
Complessivamente questi dati sembrano indicare che Wnt5a ha il ruolo di promuovere l’espansione e il mantenimento di questo tipo cellulare e quindi di perpetuare il danno tissutale e l’infiammazione cronica intestinale in RCU.
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Ackers, Ian. "Characterization and Mechanisms of WNT Signaling in Macrophages and Vascular Smooth Muscle Cells in the Atherosclerotic Plaque." Ohio University / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1556702578855203.
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Lutze, Grit [Verfasser], Jörg [Akademischer Betreuer] Wilting, Jörg [Gutachter] Wilting, and Ahmed [Gutachter] Mansouri. "Regulation of lymphangiogenesis by WNT siganlling: Focus on WNT5A / Grit Lutze ; Gutachter: Jörg Wilting, Ahmed Mansouri ; Betreuer: Jörg Wilting." Göttingen : Niedersächsische Staats- und Universitätsbibliothek Göttingen, 2019. http://d-nb.info/1177361841/34.
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Erdmann, Lara [Verfasser], Albrecht [Gutachter] Bufe, and Hans-Werner [Gutachter] Duchna. "Charakterisierung des Wnt5a-Signalwegs im chronischen OVA-Asthma-Modell / Lara Erdmann ; Gutachter: Albrecht Bufe, Hans-Werner Duchna ; Medizinische Fakultät." Bochum : Ruhr-Universität Bochum, 2019. http://d-nb.info/1193252539/34.
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Haarmann, Anna [Verfasser], Jörg [Akademischer Betreuer] Wilting, Edmone [Gutachter] Roffael, and Claudia [Gutachter] Binder. "Proliferationsuntersuchungen zur Entwicklung des Lymphgefäßsystems bei Wnt5a-transgenen Mäusen / Anna Haarmann ; Gutachter: Edmone Roffael, Claudia Binder ; Betreuer: Jörg Wilting." Göttingen : Niedersächsische Staats- und Universitätsbibliothek Göttingen, 2018. http://d-nb.info/1159768897/34.
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Almeida, Fernanda Campos Sousa de. "Localização dos transcritos dos genes WNT5A e HOXB5 em carcinomas epidermóides de boca através da técnica de hibridização in situ." Universidade de São Paulo, 2004. http://www.teses.usp.br/teses/disponiveis/23/23141/tde-21012005-105725/.
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São freqüentes alterações em vias de sinalização de genes de desenvolvimento, no que diz respeito ao carcinoma epidermóide de boca (CEB). Vinte e nove casos de CEB e tecido não tumoral adjacente à neoplasia foram investigados através da técnica de hibridização in situ. Os transcritos dos genes WNT5A e HOXB5 foram observados em todos os casos de tumor. A hibridização in situ revelou que o WNT5A estava mais expresso em tumores bem diferenciados. Adicionalmente, observou-se transcritos do WNT5A em glândulas salivares menores, estroma glandular, estroma tumoral e alguns vasos sanguíneos Entretanto, com respeito ao HOXB5 não foi possível estabelecer mudança do padrão do transcrito nos diferentes graus histológicos nas amostras de CEB. O HOXB5 também pôde ser identificado em alguns fragmentos de glândulas salivares menores, tecido muscular e em endotélio. Os resultados do presente estudo sugerem que a expressão dos genes WNT5A e HOXB5 podem estar relacionadas com a diferenciação e progressão do câncer de boca.<br>Disruption in developmental genes pathway are common in oral squamous cell carcinoma (OSCC). This study investigated the pattern of expression of two developmental genes, WNT5A and HOXB5, in 29 cases of OSCC and adjacent non tumoural tissue using in situ hybridization technique. Transcripts for WNT5A and HOXB5 were detected in all tumoral samples. In situ hybridization technique demonstrated that WNT5A transcripts were mainly detected in well differentiated tumors when compared with moderately and undifferentiated OSCC. WNT5A transcripts were also observed in accessory salivary glands, glandular stroma, and vessels. Therefore, for the HOXB5 transcript it was not possible to stability a relationship with the tumoral histological grade. The expression of HOXB5 transcripts in non tumoral samples was detected in salivary glands, glandular stroma, endothelium, and muscle. Results suggest that WNT5A and HOXB5 genes play a possible role in tumor differentiation and cancer progression.
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Barrott, Jared James. "Wnt5a Signaling Independently of the Planar Cell Polarity Pathway Resulting in Convergent Extension and Neural Tube Closure During Vertebrate Development." Diss., CLICK HERE for online access, 2008. http://contentdm.lib.byu.edu/ETD/image/etd2612.pdf.
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König, Simone [Verfasser], Heidi [Akademischer Betreuer] Hahn, Matthias [Akademischer Betreuer] Dobbelstein, and Felix [Akademischer Betreuer] Brembeck. "Die Rolle von Wnt5a bei der Regression des Basalzellkarzinoms / Simone König. Gutachter: Heidi Hahn ; Matthias Dobbelstein ; Felix Brembeck. Betreuer: Heidi Hahn." Göttingen : Niedersächsische Staats- und Universitätsbibliothek Göttingen, 2013. http://d-nb.info/1044172088/34.
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Cha, Jeeyeon. "The role of muscle segment homeobox genes in early pregnancy events." University of Cincinnati / OhioLINK, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1377871689.
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Winkelmann, Ruben Raphael [Verfasser], Matthias [Akademischer Betreuer] Laudes, and Ulrich [Gutachter] Mrowietz. "Die Rolle von wnt5a und sFRP5 in der Pathogenese verschiedener chronisch entzündlicher Erkrankungen / Ruben Raphael Winkelmann ; Gutachter: Ulrich Mrowietz ; Betreuer: Matthias Laudes." Kiel : Universitätsbibliothek Kiel, 2020. http://d-nb.info/1239114494/34.
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Diepenbruck, Sabine [Verfasser], and Peter [Akademischer Betreuer] Nelson. "The potential impact of Wnt5a on differentiation and phenotype of dendritic cells found in renal cell carcinoma / Sabine Diepenbruck ; Betreuer: Peter Nelson." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2017. http://d-nb.info/1148276033/34.
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Schreck, Christina Verfasser], Angelika [Akademischer Betreuer] [Schnieke, and Robert A. J. [Akademischer Betreuer] Oostendorp. "The role of Wnt5a in hematopoiesis and leukemia / Christina Schreck. Betreuer: Robert A. J. Oostendorp. Gutachter: Angelika Schnieke ; Robert A. J. Oostendorp." München : Universitätsbibliothek der TU München, 2015. http://d-nb.info/1084213044/34.
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Ling, Irving Teck-Cheng. "Non-canonical Wnt signalling in craniofacial skeletogenesis : role of wls, gpc4, wnt5b and wnt9a." Thesis, University of Glasgow, 2018. http://theses.gla.ac.uk/8975/.
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Craniofacial development requires progressive morphologic change, proliferation, differentiation and organization of chondrocytes preceding osteogenesis. The Wnt signalling pathway has been involved in regulating bone development and maintenance. As they are fated to become bone, chondrocytes require Wnt to polarize and orientate appropriately to initiate the endochondral ossification program. Although the canonical Wnt signalling has been studied in the context of bone development, the effects of non-canonical Wnt signalling in regulating the timing of cartilage maturation and subsequent bone formation in shaping ventral craniofacial structure is not well understood. In this thesis, I examined the role of the non-canonical Wnt signalling pathway (through the study of the role of wls, gpc4, wnt5b and wnt9a) in regulating zebrafish Meckel’s cartilage maturation to the onset of osteogenic differentiation. First, I show that disruption of wls resulted in a significant loss of craniofacial bone, whereas lack of gpc4, wnt5b and wnt9a resulted in severely delayed endochondral ossification. This demonstrates the importance of the non-canonical Wnt pathway in regulating coordinated ventral cartilage morphogenesis by directing chondrocyte polarity. Second, I found distinct cellular requirements within the body and midzone of the mandible. Without non-canonical Wnt signalling, chondrocytes within the midzone appear to remain in their prehypertrophic state and fail to elongate and stack. This may suggest the importance of Wnt signalling in determining jaw length and size. Third, I generated a double transgenic zebrabow line to allow cellular studies on dynamic cell behaviour during development. Finally, to further interrogate the role of Wnt signalling during chondrocyte maturation, I studied the role of intracellular Wnt trafficking. More recently, there has been increasing evidence that Wnt activity is not only regulated in the receiving cells but also on the level of its secretion (Gross and Boutros, 2013). By studying wntless (wls), a multi-transmembrane protein that shuttles Wnts from the Golgi to the plasma membrane, I found that wls trafficking through coat protein vesicles (COP) is key in neural crest specification and differentiation. These works provide important insights into the non-canonical Wnt signalling during endochondral bone formation and craniofacial lower jaw development.
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Kmetzsch, Kate E. "Molecular and Cellular Mechanisms Whereby the Apical Ectodermal Ridge (AER), Via Wnt5a, Mediates Directional Migration of the Adjacent Mesenchyme During Vertebrate Limb Development." Diss., CLICK HERE for online access, 2009. http://contentdm.lib.byu.edu/ETD/image/etd3136.pdf.
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Doroudi, Maryam. "Essential roles of Pdia3/PLAA receptor complex and CaMKII IN 1α,25(OH)₂D₃ and Wnt5a calcium-dependent signaling pathways in osteoblasts and chondrocytes". Diss., Georgia Institute of Technology, 2014. http://hdl.handle.net/1853/53427.
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The vitamin D metabolite 1,25-dihydroxyvitamin D3 [1α,25(OH)2D3] plays an important role in the regulation of musculoskeletal growth and differentiation. 1α,25(OH)2D3 mediates its effects on cells, including chondrocytes and osteoblasts, through the classical nuclear 1α,25(OH)2D3 receptor. Additionally, recent evidence indicates that several cellular responses to 1α,25(OH)2D3 are mediated via a rapid, calcium-dependent membrane-mediated pathway. These actions of 1α,25(OH)2D3 can be blocked by antibodies to protein-disulfide isomerase family A, member 3 (Pdia3), indicating that it is part of the receptor complex; however, the pathway which is activated by this receptor is not fully understood. The overall goal of this thesis was to examine the roles of phospholipase A2 activating protein (PLAA) and calcium calmodulin-dependent kinase II (CaMKII) in 1α,25(OH)2D3 rapid membrane-mediated signaling. We further investigated the interaction between two pathways regulating growth plate cartilage and endochondral bone formation, 1α,25(OH)2D3 and Wnt5a, at the receptor complex level. Results indicated that PLAA was required for mediating 1α,25(OH)2D3 signal from Pdia3. Furthermore, CaM and CaMKII were identified as mediators of 1α,25(OH)2D3-stimulated PLAA-dependent activation of cPLA2 and PKCα, and downstream biological effects. Wnt5a and 1α,25(OH)2D3 are important regulators of endochondral bone formation. This study demonstrated that 1α,25(OH)2D3 and Wnt5a mediate their effects via similar receptor components in osteoblasts and chondrocytes suggesting that these pathways may interact.
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Valentin, Julia Maria [Verfasser]. "Molekulare Untersuchung anti-entzündlicher Effekte von Omega-3-Fettsäuren auf wnt5a in Patienten mit gastrointestinalem oder urologischem Karzinom: eine randomisierte, kontrollierte Studie. / Julia Maria Valentin." Kiel : Universitätsbibliothek Kiel, 2019. http://d-nb.info/1196090912/34.
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Chen, Chih-Wei [Verfasser], Alexandra [Gutachter] Schambony та Georg [Gutachter] Schett. "Non-canonical WNT5A promotes tissue fibrosis by JNK-dependent activation of latent TGF-β in Systemic Sclerosis / Chih-Wei Chen ; Gutachter: Alexandra Schambony, Georg Schett". Erlangen : Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 2017. http://d-nb.info/115096443X/34.
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Mahoney, Emilia. "Molecular Alterations in Bone Development and Bone Tumorigenesis." The Ohio State University, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=osu1243957525.
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Mlih, Mohamed. "Implication de LRP1 et ShcA dans deux pathologies cardiovasculaires : l'arthérosclérose et l'insuffisance cardiaque." Thesis, Strasbourg, 2012. http://www.theses.fr/2012STRAJ086/document.
Full textAbstract:
Les maladies cardiovasculaires sont la première cause de mortalité dans le monde. Une meilleure compréhension des mécanismes physiopathologiques est nécessaire. Dans ce travail de thèse nous nous sommes intéressés à deux pathologies cardiovasculaires : l’athérosclérose et l’insuffisance cardiaque. Récemment, nous avons identifié le récepteur LRP1 et la protéine adaptatrice ShcA comme étant deux protéines impliquées dans deux de ces pathologies cardiovasculaires. Nousavons montré que ShcA joue un rôle protecteur dans l’insuffisance cardiaque. Chez les souris déficientes en ShcA au niveau cardiaque, nous observons une cardiomyopathie caractérisée par une dilatation du ventricule gauche associée à une perte de la contractilité. Nous avons montré que ShcA est essentiel à l’organisation des sarcomères et ceci très tôt durant l’embryogenèse. Dans une deuxième partie nous avons montré qu’en l’absence de PPARgamma, LRP1 était nécessaire à la calcification vasculaire en activant la voie prochondrogénique de Wnt5a. Nous avons montré que PPARgamma protège de la calcification vasculaire en induisant l’expression de Sfrp2 qui agit comme un antagoniste de Wnt5a<br>Cardiovascular disease is the number one cause of death worldwide. A better understanding of the pathophysiological mechanisms is necessary. In this thesis we are focused on two cardiovascular diseases: atherosclerosis and heart failure. Recently, we identified the LRP1 receptor and the adapter protein ShcA as two proteins involved in two of these cardiovascular diseases. We have shown that ShcA exerts a protective role against heart failure. Mutant mice lacking ShcA in the heart exhibit a dilated cardiomyopathy with reduced cardiac contractility. Myocyte ultrastructure analysis shows that Shc A is essential to maintain sarcomeric intégrity in early embryonic heart development. in last part we have shown vascular calcification in the absence of PPARgamma requires expression of LRP1 in vascular smooth muscle cells. LRP1 promotes a Wnt5a-dependent prochondrogenic pathway. We show that PPARgamma protects against vascular calcification by inducing the expression of secreted frizzled-related protein-2 (Sfrp2, wich functions as a Wnt5a antagonist
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Demanou, Toukam Jules Arnaud [Verfasser], Jörg [Akademischer Betreuer] Wilting, Jörg [Gutachter] Großhans, and Margarete [Gutachter] Schön. "Morphologische Charakterisierung von Wnt5a Knock-out-Mäusen: Eine licht- und elektronenmikroskopische Untersuchung des dermalen Lymphgefäßsystems / Jules Arnaud Demanou Toukam ; Gutachter: Jörg Großhans, Margarete Schön ; Betreuer: Jörg Wilting." Göttingen : Niedersächsische Staats- und Universitätsbibliothek Göttingen, 2019. http://d-nb.info/1188025120/34.
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Pralle, Moritz [Verfasser], and Patrick [Akademischer Betreuer] Michl. "Einfluss des Glykoproteins WNT5A auf das Apoptoseverhalten von Pankreaskarzinomzellen in vitro und In-vivo-Bildgebung von NIS-positiven Pankreaskarzinom-Xenografts in Nacktmäusen / Moritz Pralle. Betreuer: Patrick Michl." Marburg : Philipps-Universität Marburg, 2014. http://d-nb.info/1051934540/34.
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