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Artykuły w czasopismach na temat „Membrane-Bound TGF-Β”

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Data publikacji: 30 listopada 2024
Data aktualizacji: 31 lipca 2025

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1

Elderbroom, Jennifer L., Jennifer J. Huang, Catherine E. Gatza та ін. "Ectodomain shedding of TβRIII is required for TβRIII-mediated suppression of TGF-β signaling and breast cancer migration and invasion". Molecular Biology of the Cell 25, № 16 (2014): 2320–32. http://dx.doi.org/10.1091/mbc.e13-09-0524.

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The type III transforming growth factor β (TGF-β) receptor (TβRIII), also known as betaglycan, is the most abundantly expressed TGF-β receptor. TβRIII suppresses breast cancer progression by inhibiting migration, invasion, metastasis, and angiogenesis. TβRIII binds TGF-β ligands, with membrane-bound TβRIII presenting ligand to enhance TGF-β signaling. However, TβRIII can also undergo ectodomain shedding, releasing soluble TβRIII, which binds and sequesters ligand to inhibit downstream signaling. To investigate the relative contributions of soluble and membrane-bound TβRIII on TGF-β signaling a
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2

Kim, Pyeung-Hyeun, Young-Saeng Jang, Ha-Eon Song, et al. "Mechanism underlying the induction of Foxp3+ regulatory T cells by lactoferrin." Journal of Immunology 200, no. 1_Supplement (2018): 47.16. http://dx.doi.org/10.4049/jimmunol.200.supp.47.16.

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Abstract Lactoferrin (LF) is multifunctional in the immune response. We have previously demonstrated that LF acts like TGF-β in IgA B cell differentiation. Therein, we explored whether LF affects peripheral regulatory T cell (Treg) differentiation. Indeed, LF induced Foxp3+ Treg differentiation by itself and in combination with TGF-β1 synergized to express Foxp3. It was conceivable that LF may increase Foxp3 expression through secretion of active TGF-β or facilitating latent TGF-β to active form. There was little active TGF-β in the supernatant from LF-stimulated T cells. Surprisingly, however
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3

Yan, Xiaohua, та Ye-Guang Chen. "Smad7: not only a regulator, but also a cross-talk mediator of TGF-β signalling". Biochemical Journal 434, № 1 (2011): 1–10. http://dx.doi.org/10.1042/bj20101827.

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TGF-β (transforming growth factor-β) is a pleiotropic cytokine regulating diverse cellular processes. It signals through membrane-bound receptors, downstream Smad proteins and/or other signalling mediators. Smad7 has been well established to be a key negative regulator of TGF-β signalling. It antagonizes TGF-β signalling through multiple mechanisms in the cytoplasm and in the nucleus. Smad7 can be transcriptionally induced by TGF-β and other growth factors and serves as an important cross-talk mediator of the TGF-β signalling pathway with other signalling pathways. Accordingly, it plays pivota
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4

Kim, Sun Kyung, Morkos A. Henen, and Andrew P. Hinck. "Structural biology of betaglycan and endoglin, membrane-bound co-receptors of the TGF-beta family." Experimental Biology and Medicine 244, no. 17 (2019): 1547–58. http://dx.doi.org/10.1177/1535370219881160.

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Betaglycan and endoglin, membrane-bound co-receptors of the TGF-β family, are required to mediate the signaling of a select subset of TGF-β family ligands, TGF-β2 and InhA, and BMP-9 and BMP-10, respectively. Previous biochemical and biophysical methods suggested alternative modes of ligand binding might be responsible for these co-receptors to selectively recognize and potentiate the functions of their ligands, yet the molecular details were lacking. Recent progress determining structures of betaglycan and endoglin, both alone and as bound to their cognate ligands, is presented herein. The st
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5

Sisto, Margherita, Domenico Ribatti, and Sabrina Lisi. "SMADS-Mediate Molecular Mechanisms in Sjögren’s Syndrome." International Journal of Molecular Sciences 22, no. 6 (2021): 3203. http://dx.doi.org/10.3390/ijms22063203.

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There is considerable interest in delineating the molecular mechanisms of action of transforming growth factor-β (TGF-β), considered as central player in a plethora of human conditions, including cancer, fibrosis and autoimmune disease. TGF-β elicits its biological effects through membrane bound serine/threonine kinase receptors which transmit their signals via downstream signalling molecules, SMADs, which regulate the transcription of target genes in collaboration with various co-activators and co-repressors. Until now, therapeutic strategy for primary Sjögren’s syndrome (pSS) has been focuse
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6

Weber, Florian, Oliver Treeck, Patricia Mester, and Christa Buechler. "Expression and Function of BMP and Activin Membrane-Bound Inhibitor (BAMBI) in Chronic Liver Diseases and Hepatocellular Carcinoma." International Journal of Molecular Sciences 24, no. 4 (2023): 3473. http://dx.doi.org/10.3390/ijms24043473.

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BAMBI (bone morphogenetic protein and activin membrane-bound inhibitor) is a transmembrane pseudoreceptor structurally related to transforming growth factor (TGF)-β type 1 receptors (TGF-β1Rs). BAMBI lacks a kinase domain and functions as a TGF-β1R antagonist. Essential processes such as cell differentiation and proliferation are regulated by TGF-β1R signaling. TGF-β is the best-studied ligand of TGF-βRs and has an eminent role in inflammation and fibrogenesis. Liver fibrosis is the end stage of almost all chronic liver diseases, such as non-alcoholic fatty liver disease, and at the moment, th
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7

Dhandapani, Krishnan M., F. Marlene Wade, Virendra B. Mahesh та Darrell W. Brann. "Astrocyte-Derived Transforming Growth Factor-β Mediates the Neuroprotective Effects of 17β-Estradiol: Involvement of Nonclassical Genomic Signaling Pathways". Endocrinology 146, № 6 (2005): 2749–59. http://dx.doi.org/10.1210/en.2005-0014.

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Abstract 17β-Estradiol (E2) and selective estrogen receptor modulators (SERMs), such as tamoxifen, mediate numerous effects in the brain, including neurosecretion, neuroprotection, and the induction of synaptic plasticity. Astrocytes, the most abundant cell type in the brain, influence many of these same functions and thus may represent a mediator of estrogen action. The present study examined the regulatory effect and underlying cell signaling mechanisms of E2-induced release of neurotropic growth factors from primary rat cortical astrocyte cultures. The results revealed that E2 (0.5, 1, and
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8

Gallardo-Vara, Ruiz-Llorente, Casado-Vela, et al. "Endoglin Protein Interactome Profiling Identifies TRIM21 and Galectin-3 as New Binding Partners." Cells 8, no. 9 (2019): 1082. http://dx.doi.org/10.3390/cells8091082.

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Endoglin is a 180-kDa glycoprotein receptor primarily expressed by the vascular endothelium and involved in cardiovascular disease and cancer. Heterozygous mutations in the endoglin gene (ENG) cause hereditary hemorrhagic telangiectasia type 1, a vascular disease that presents with nasal and gastrointestinal bleeding, skin and mucosa telangiectases, and arteriovenous malformations in internal organs. A circulating form of endoglin (alias soluble endoglin, sEng), proteolytically released from the membrane-bound protein, has been observed in several inflammation-related pathological conditions a
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9

Zhu, Qingwei, Yong Hwan Kim, Douglas Wang, S. Paul Oh, and Kunxin Luo. "SnoN facilitates ALK1–Smad1/5 signaling during embryonic angiogenesis." Journal of Cell Biology 202, no. 6 (2013): 937–50. http://dx.doi.org/10.1083/jcb.201208113.

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In endothelial cells, two type I receptors of the transforming growth factor β (TGF-β) family, ALK1 and ALK5, coordinate to regulate embryonic angiogenesis in response to BMP9/10 and TGF-β. Whereas TGF-β binds to and activates ALK5, leading to Smad2/3 phosphorylation and inhibition of endothelial cell proliferation and migration, BMP9/10 and TGF-β also bind to ALK1, resulting in the activation of Smad1/5. SnoN is a negative regulator of ALK5 signaling through the binding and repression of Smad2/3. Here we uncover a positive role of SnoN in enhancing Smad1/5 activation in endothelial cells to p
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10

Yang, Young, та Sujeong Park. "Abstract LB010: LY6K depletion modulates TGF-β and EGF signaling". Cancer Research 83, № 8_Supplement (2023): LB010. http://dx.doi.org/10.1158/1538-7445.am2023-lb010.

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Abstract Lymphocyte antigen 6 complex locus K (LY6K), a glycosylphosphatidylinositol-anchored protein, plays a dynamic role in cancer metastasis. In the current study, we deciphered the effects of LY6K on transforming growth factor-β (TGF-β) and epidermal growth factor (EGF) signaling through clathrin- and caveolin-1 (CAV-1)-mediated endocytosis. LY6K expression level is elevated in higher grade cervical cancer patients correlating with poor overall survival, progression-free survival, and disease-free survival. LY6K-depletion in HeLa and SiHa cancer cells suppressed EGF-induced proliferation
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11

Juárez, Patricia, M. Magdalena Vilchis-Landeros, José Ponce-Coria, et al. "Soluble betaglycan reduces renal damage progression in db/db mice." American Journal of Physiology-Renal Physiology 292, no. 1 (2007): F321—F329. http://dx.doi.org/10.1152/ajprenal.00264.2006.

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Transforming growth factor-β (TGF-β) is a key mediator in the pathogenesis of renal diseases. Betaglycan, also known as the type III TGF-β receptor, regulates TGF-β action by modulating its access to the type I and II receptors. Betaglycan potentiates TGF-β; however, soluble betaglycan, which is produced by the shedding of the membrane-bound receptor, is a potent antagonist of TGF-β. In the present work, we have used a recombinant form of soluble betaglycan (SBG) to prevent renal damage in genetically obese and diabetic db/db mice. Eight-wk-old db/db or nondiabetic ( db/m) mice were injected i
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12

Jang, Young-Saeng, Ha-Eon Song, Goo-Young Seo та ін. "Lactoferrin Potentiates Inducible Regulatory T Cell Differentiation through TGF-β Receptor III Binding and Activation of Membrane-Bound TGF-β". Journal of Immunology 207, № 10 (2021): 2456–64. http://dx.doi.org/10.4049/jimmunol.2100326.

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13

Jonuleit, Helmut, Edgar Schmitt, Hacer Kakirman, Michael Stassen, Jürgen Knop, and Alexander H. Enk. "Infectious Tolerance." Journal of Experimental Medicine 196, no. 2 (2002): 255–60. http://dx.doi.org/10.1084/jem.20020394.

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Regulatory CD4+CD25+ T cells (Treg) are mandatory for maintaining immunologic self-tolerance. We demonstrate that the cell-cell contact–mediated suppression of conventional CD4+ T cells by human CD25+ Treg cells is fixation resistant, independent from membrane-bound TGF-β but requires activation and protein synthesis of CD25+ Treg cells. Coactivation of CD25+ Treg cells with Treg cell–depleted CD4+ T cells results in anergized CD4+ T cells that in turn inhibit the activation of conventional, freshly isolated CD4+ T helper (Th) cells. This infectious suppressive activity, transferred from CD25+
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14

Koinuma, Daizo, Shuichi Tsutsumi, Naoko Kamimura та ін. "Chromatin Immunoprecipitation on Microarray Analysis of Smad2/3 Binding Sites Reveals Roles of ETS1 and TFAP2A in Transforming Growth Factor β Signaling". Molecular and Cellular Biology 29, № 1 (2008): 172–86. http://dx.doi.org/10.1128/mcb.01038-08.

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ABSTRACT The Smad2 and Smad3 (Smad2/3) proteins are principally involved in the transmission of transforming growth factor β (TGF-β) signaling from the plasma membrane to the nucleus. Many transcription factors have been shown to cooperate with the Smad2/3 proteins in regulating the transcription of target genes, enabling appropriate gene expression by cells. Here we identified 1,787 Smad2/3 binding sites in the promoter regions of over 25,500 genes by chromatin immunoprecipitation on microarray in HaCaT keratinocytes. Binding elements for the v-ets erythroblastosis virus E26 oncogene homolog
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15

Kudipudi, Pradeep K., Sebastian P. Galuska, Raimund Dietze, Georgios Scheiner-Bobis, Kate L. Loveland та Lutz Konrad. "Betaglycan (TβRIII) is a Key Factor in TGF-β2 Signaling in Prepubertal Rat Sertoli Cells". International Journal of Molecular Sciences 20, № 24 (2019): 6214. http://dx.doi.org/10.3390/ijms20246214.

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Transforming growth factor-βs (TGF-βs) signal after binding to the TGF-β receptors TβRI and TβRII. Recently, however, betaglycan (BG) was identified as an important co-receptor, especially for TGF-β2. Both proteins are involved in several testicular functions. Thus, we analyzed the importance of BG for TGF-β1/2 signaling in Sertoli cells with ELISAs, qRT-PCR, siRNA silencing and BrdU assays. TGF-β1 as well as TGF-β2 reduced shedding of membrane-bound BG (mBG), thus reducing the amount of soluble BG (sBG), which is often an antagonist to TGF-β signaling. Treatment of Sertoli cells with GM6001,
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16

Bardhan, Kankana, Nikolaos Patsoukis, Alexandra Plessa, et al. "Rap1-GTP Augments TGF-b-Mediated Signaling in T Lymphocytes Via a Mechanism Dependent on the b Chain of LFA-1 Integrin." Blood 126, no. 23 (2015): 3422. http://dx.doi.org/10.1182/blood.v126.23.3422.3422.

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Abstract Integrin-mediated adhesion of lymphocytes to antigen presenting cells (APCs) is a critical event linking innate and adaptive immunity. Integrins function as bidirectional receptors and can transmit signals from both sides of the plasma membrane, a property referred to as inside-out and outside-in signaling. Lymphocyte adhesion to APC is mainly accomplished through the principle adhesion molecule on the lymphocyte surface, the lymphocyte functional antigen 1 (LFA-1), which binds to intercellular adhesion molecule 1 (ICAM-1) on the surface of APCs. In order to mediate its function, LFA-
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17

Bandura-Morgan, Laura, Esma Yolcu, Hong Zhao, Shravan Madireddi та Haval Shirwan. "SA-FasL-Induced Localized Allotolerance to Pancreatic Islets Is Mediated by Phagocytes/TGF-β Axis (145.6)". Journal of Immunology 184, № 1_Supplement (2010): 145.6. http://dx.doi.org/10.4049/jimmunol.184.supp.145.6.

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Abstract We recently showed that pancreatic islets engineered to display on their surface a recombinant SA-FasL protein induce robust localized tolerance. Tolerance was initiated by FasL-induced alloreactive T cell apoptosis and sustained by Treg cells. We herein tested if tolerance induction involves phagocytes engulfing T cells apoptotic bodies as a means of regulation. C57BL/6 mice were transplanted with BALB/c SA-FasL-islets with the transient use of rapamycin given on the day of Tx daily for 15 days. The role of phagocytes and TGF-β in the induced tolerance was tested by using clodronate-
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18

Hauri-Hohl, Mathias M., Saulius Zuklys, Marcel P. Keller та ін. "TGF-β signaling in thymic epithelial cells regulates thymic involution and postirradiation reconstitution". Blood 112, № 3 (2008): 626–34. http://dx.doi.org/10.1182/blood-2007-10-115618.

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Abstract The thymus constitutes the primary lymphoid organ responsible for the generation of naive T cells. Its stromal compartment is largely composed of a scaffold of different subsets of epithelial cells that provide soluble and membrane-bound molecules essential for thymocyte maturation and selection. With senescence, a steady decline in the thymic output of T cells has been observed. Numeric and qualitative changes in the stromal compartment of the thymus resulting in reduced thymopoietic capacity have been suggested to account for this physiologic process. The precise cellular and molecu
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19

Vega, Jose L., Daniel Saban, Yejun Carrier, Sharmila Masli та Howard L. Weiner. "Retinal Pigment Epithelial Cells Induce foxp3+Regulatory T Cells via Membrane-bound TGF-β". Ocular Immunology and Inflammation 18, № 6 (2010): 459–69. http://dx.doi.org/10.3109/09273948.2010.509532.

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20

Verma, Amit, Tony A. Navas, Jing Ying, et al. "SD-208, a Novel Transforming Growth Factor Beta Receptor I Kinase Inhibitor, Can Stimulate Hematopoiesis in Myelodysplastic Syndrome Progenitors." Blood 106, no. 11 (2005): 3448. http://dx.doi.org/10.1182/blood.v106.11.3448.3448.

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Abstract Transforming Growth Factor β (TGF-β) is a myelosuppressive cytokine that has been implicated in the ineffective hematopoiesis seen in myelodysplastic syndromes (MDS). Overactivation of TGF-β signaling in this disease was demonstrated immunohistochemically by significantly higher nuclear SMAD2 phosphorylation observed in 20 MDS bone marrows when compared with 7 non MDS anemic controls (P < 0.0001, 2 Tailed T Test, Image Pro Plus software). This data along with high levels of membrane-bound and plasma TGF-β observed in MDS patients in previous studies support the development of t
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21

Pfeifer, Christian G., Alexandra Karl, Arne Berner, et al. "Expression of BMP and Actin Membrane Bound Inhibitor Is Increased during Terminal Differentiation of MSCs." Stem Cells International 2016 (2016): 1–9. http://dx.doi.org/10.1155/2016/2685147.

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Chondrogenic differentiating mesenchymal stem cells (MSCs) are mimicking embryonal endochondral ossification and become hypertrophic. BMP (bone morphogenetic protein) and Activin Membrane Bound Inhibitor (BAMBI) is a pseudoreceptor that regulates the activity of transforming growth factor-β(TGF-β) and BMP signalling during chondrogenesis. Both TGF-βand BMP signalling are regulators of chondrogenic cell differentiation. Human bone marrow derived MSCs were chondrogenically predifferentiated in aggregate culture for 14 days. Thereafter, one group was subjected to hypertrophy enhancing media condi
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22

Greulich, Benjamin M., John Pawlak, John Post, Elena Karas та Gerard Blobe. "Abstract 6964: Regulation of TGF-β signaling via a novel TβRIII sheddase". Cancer Research 84, № 6_Supplement (2024): 6964. http://dx.doi.org/10.1158/1538-7445.am2024-6964.

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Abstract In a normal cell, TGF-β signaling serves as a tumor suppressor by reducing proliferation and promoting apoptosis. Paradoxically, the function of TGF-β signaling reverses in a cancer cell and begins to promote oncogenic pathways such as proliferation, survival, evasion of the immune system, and epithelial to mesenchymal transition (EMT). This has made TGF-β signaling a very attractive therapeutic target for a wide variety of human carcinomas. As a result, many small molecule inhibitors of TGF-β signaling have been developed, but none have achieved FDA approval for use in human cancers
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23

Guizzardi, Stefano, Giuseppe Pedrazzi, and Carlo Galli. "Low Frequency Electromagnetic Fields Might Increase the Effect of Enamel Matrix Derivative on Periodontal Tissues." Applied Sciences 11, no. 22 (2021): 10758. http://dx.doi.org/10.3390/app112210758.

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Periodontal regeneration is a complex goal, which is commonly pursued with a combination of surgical techniques, biomaterials, and bioactive compounds. One such compound is enamel matrix derivative (EMD), a medical substance that is extracted from porcine tooth germs and which contains several protein fractions with BMP- and TGF-β-like action. Activation of TGF-β signaling is required for EMD activity on cells and tissues, and a growing body of evidence indicates that EMD largely relies on this pathway. As low frequency electromagnetic fields (EMFs) have long been investigated as a tool to pro
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24

Lynch, M. A., T. A. Petrel, H. Song та ін. "Responsiveness to Transforming Growth Factor-β (TGF-β)-Mediated Growth Inhibition Is a Function of Membrane-Bound TGF-β Type II Receptor in Human Breast Cancer Cells". Gene Expression 9, № 4 (2001): 157–71. http://dx.doi.org/10.3727/000000001783992560.

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Eill, Elizabeth, та Steven M. Taffet. "IL-10 and TGF- β differentially regulate gap junction formation and membrane transfer in macrophages and macrophage-like cells". Journal of Immunology 202, № 1_Supplement (2019): 58.19. http://dx.doi.org/10.4049/jimmunol.202.supp.58.19.

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Abstract In macrophages, the expression and regulation of the gap junction protein connexin43 (Cx43) is poorly understood. Here we demonstrate that inflammatory and anti-inflammatory mediators differentially regulate gap junction plaque formation in primary bone marrow-derived macrophages (BMDMs) and the macrophage-like cell line RAW264.7. RAW264.7 macrophage-like cells were transfected with GFP-tagged Cx43 to visualize Cx43 trafficking. LPS, an inflammatory mediator, is a potent inducer of Cx43 in BMDMs and RAW264-Cx43-GFP but demonstrates limited trafficking into gap junction plaques. Intere
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26

Patsoukis, Nikolaos, Lequn Li та Vassiliki A. Boussiotis. "Rap1-GTP Augments Activation of Smad and p38 Mediated Signaling Downstream of TGF-β Receptor In T Lymphocytes". Blood 116, № 21 (2010): 956. http://dx.doi.org/10.1182/blood.v116.21.956.956.

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Abstract Abstract 956 Rap1A, a member of the Ras superfamily, was discovered as a gene product that reverted K-Ras-induced transformation. Although it was initially thought that Rap1A (thereafter referred to as Rap1) opposes Ras-induced transformation by competing for common downstream effector(s), it has now become apparent that Ras and Rap1 proteins operate in different signaling networks and mediate distinct functions. In lymphocytes Rap1 is activated by BCR and TCR mediated signals and is involved in inside-out activation of integrins. To understand the role of Rap1 in T cell responses we
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27

Ostroukhova, Marina, Carole Seguin-Devaux, Timothy B. Oriss та ін. "Tolerance induced by inhaled antigen involves CD4+ T cells expressing membrane-bound TGF-β and FOXP3". Journal of Clinical Investigation 114, № 1 (2004): 28–38. http://dx.doi.org/10.1172/jci200420509.

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Wang, Hong-Min, Zhe Zhou, Jie Miao, et al. "Membrane Bound CRT Fragment Accelerates Tumor Growth of Melanoma B16 Cell In Vivo through Promoting M2 Polarization via TLR4." Journal of Immunology Research 2022 (October 6, 2022): 1–12. http://dx.doi.org/10.1155/2022/4626813.

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Calreticulin (CRT) is a major calcium-binding luminal resident protein on the endoplasmic reticulum that can also be released extracellular as well as anchored on surface of cells. Previously, we demonstrated that soluble recombinant CRT fragment 39-272 (CRT/39-272) exhibited potent immunostimulatory effects as well as immunoregulation effects on immune cells. Here, we constructed stable B16 melanoma cell lines expressing recombinant CRT/39-272 on the membrane (B16-tmCRT/39-272) to investigate the roles of cell surface CRT on tumor progression. We found that B16-tmCRT/39-272 cells subcutaneous
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29

Hyytiäinen, Marko, та Jorma Keski-Oja. "Latent TGF-β binding protein LTBP-2 decreases fibroblast adhesion to fibronectin". Journal of Cell Biology 163, № 6 (2003): 1363–74. http://dx.doi.org/10.1083/jcb.200309105.

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We have analyzed the effects of latent TGF-β binding protein 2 (LTBP-2) and its fragments on lung fibroblast adhesion. Quantitative cell adhesion assays indicated that fibroblasts do not adhere to full-length LTBP-2. Interestingly, LTBP-2 had dominant disrupting effects on the morphology of fibroblasts adhering to fibronectin (FN). Fibroblasts plated on LTBP-2 and FN substratum exhibited less adherent morphology and displayed clearly decreased actin stress fibers than cells plated on FN. These cells formed, instead, extensive membrane ruffles. LTBP-2 had no effects on cells adhering to collage
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30

Payet, Melissa, Franck Ah-Pine, Xavier Guillot, and Philippe Gasque. "Inflammatory Mesenchymal Stem Cells Express Abundant Membrane-Bound and Soluble Forms of C-Type Lectin-like CD248." International Journal of Molecular Sciences 24, no. 11 (2023): 9546. http://dx.doi.org/10.3390/ijms24119546.

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CD248 (endosialin) belongs to a glycoprotein family that also includes thrombomodulin (CD141), CLEC14A, and CD93 (AA4) stem cell markers. We analyzed the regulated expression of CD248 in vitro using skin (HFFF) and synovial (FLS) mesenchymal stem cell lines, and in fluid and tissue samples of rheumatoid arthritis (RA) and osteoarthritis (OA) patients. Cells were incubated with either rhVEGF165, bFGF, TGF-β1, IL1-β, TNF-α, TGFβ1, IFN-γ, or PMA (Phorbol ester). There was no statistically significant change in membrane expression. A soluble (s) form of cleaved CD248 (sCD248) was detected after ce
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Prud’homme, Gérald J., and Qinghua Wang. "Anti-Inflammatory Role of the Klotho Protein and Relevance to Aging." Cells 13, no. 17 (2024): 1413. http://dx.doi.org/10.3390/cells13171413.

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The α-Klotho protein (hereafter Klotho) is an obligate coreceptor for fibroblast growth factor 23 (FGF23). It is produced in the kidneys, brain and other sites. Klotho insufficiency causes hyperphosphatemia and other anomalies. Importantly, it is associated with chronic pathologies (often age-related) that have an inflammatory component. This includes atherosclerosis, diabetes and Alzheimer’s disease. Its mode of action in these diseases is not well understood, but it inhibits or regulates multiple major pathways. Klotho has a membrane form and a soluble form (s-Klotho). Cytosolic Klotho is po
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Boyiadzis, Michael, Miroslaw Szczepanski та Theresa Whiteside. "Membrane Associated TGF-β1 on Leukemia Blast-Derived Microvesicles In Sera of Acute Myeloid Leukemia Patients Suppresses NK Cell Function". Blood 116, № 21 (2010): 502. http://dx.doi.org/10.1182/blood.v116.21.502.502.

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Abstract Abstract 502 Natural killer (NK) cell cytotoxicity in patients with acute myeloid leukemia (AML) is significantly decreased relative to that in normal controls (NC). TGF-β1 is a potent inhibitor of NK cell cytotoxicity. We considered the possibility that suppression of NK cell activity in AML patients is mediated by leukemia blast-derived microvesicles (MV) via TGF-β1. Sera of 19 patients newly diagnosed with AML prior to any treatment were used to isolate MV by ultracentrifugation. MV from AML patients were positive for the blast-associated markers (CD33, CD34, CD117) by flow cytomet
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Cohen, Margo P., Fuad N. Ziyadeh, Gregory T. Lautenslager, Jonathan A. Cohen та Clyde W. Shearman. "Glycated albumin stimulation of PKC-β activity is linked to increased collagen IV in mesangial cells". American Journal of Physiology-Renal Physiology 276, № 5 (1999): F684—F690. http://dx.doi.org/10.1152/ajprenal.1999.276.5.f684.

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Albumin modified by Amadori-glucose adducts induces coordinate increases in the expression of extracellular matrix proteins, transforming growth factor (TGF)-β1, and the TGF-β type II receptor in glomerular mesangial cells. Because activation of protein kinase C (PKC) accompanies the increased mesangial cell expression of matrix proteins and TGF-β1 induced by high ambient glucose, we postulated that glycated albumin (GA) modulates PKC activity and that PKC participates in mediating the GA-induced stimulation of matrix production. To test this hypothesis, we examined the effects of PKC inhibito
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Ghiringhelli, François, Cédric Ménard, Magali Terme та ін. "CD4+CD25+ regulatory T cells inhibit natural killer cell functions in a transforming growth factor–β–dependent manner". Journal of Experimental Medicine 202, № 8 (2005): 1075–85. http://dx.doi.org/10.1084/jem.20051511.

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Tumor growth promotes the expansion of CD4+CD25+ regulatory T (T reg) cells that counteract T cell–mediated immune responses. An inverse correlation between natural killer (NK) cell activation and T reg cell expansion in tumor-bearing patients, shown here, prompted us to address the role of T reg cells in controlling innate antitumor immunity. Our experiments indicate that human T reg cells expressed membrane-bound transforming growth factor (TGF)–β, which directly inhibited NK cell effector functions and down-regulated NKG2D receptors on the NK cell surface. Adoptive transfer of wild-type T r
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Tang, Jiaqi, Cody Gifford, Rohan Samarakoon та Paul Higgins. "Deregulation of Negative Controls on TGF-β1 Signaling in Tumor Progression". Cancers 10, № 6 (2018): 159. http://dx.doi.org/10.3390/cancers10060159.

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The multi-functional cytokine transforming growth factor-β1 (TGF-β1) has growth inhibitory and anti-inflammatory roles during homeostasis and the early stages of cancer. Aberrant TGF-β activation in the late-stages of tumorigenesis, however, promotes development of aggressive growth characteristics and metastatic spread. Given the critical importance of this growth factor in fibrotic and neoplastic disorders, the TGF-β1 network is subject to extensive, multi-level negative controls that impact receptor function, mothers against decapentaplegic homolog 2/3 (SMAD2/3) activation, intracellular si
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Hsu, Hsiang-Hao, Aline Yen Ling Wang, Charles Yuen Yung Loh, Ashwin Alke Pai, and Huang-Kai Kao. "Therapeutic Potential of Exosomes Derived from Diabetic Adipose Stem Cells in Cutaneous Wound Healing of db/db Mice." Pharmaceutics 14, no. 6 (2022): 1206. http://dx.doi.org/10.3390/pharmaceutics14061206.

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(1) Background: Diabetes impairs angiogenesis and wound healing. Paracrine secretion from adipose stem cells (ASCs) contains membrane-bound nano-vesicles called exosomes (ASC-Exo) but the functional role and therapeutic potential of diabetic ASC-Exo in wound healing are unknown. This study aims to investigate the in vivo mechanistic basis by which diabetic ASC-Exo enhance cutaneous wound healing in a diabetic mouse model. (2) Methods: Topically applied exosomes could efficiently target and preferentially accumulate in wound tissue, and the cellular origin, ASC or dermal fibroblast (DFb), has n
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Zhang, Minggang, Sheng Xu, Yanmei Han та Xuetao Cao. "Apoptotic cells attenuate fulminant hepatitis by priming Kupffer cells to produce interleukin-10 through membrane-bound TGF-β". Hepatology 53, № 1 (2010): 306–16. http://dx.doi.org/10.1002/hep.24029.

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Devocelle, Aurore, Lola Lecru, Hélène François та ін. "Inhibition of TGF-β1 Signaling by IL-15: A Novel Role for IL-15 in the Control of Renal Epithelial-Mesenchymal Transition: IL-15 Counteracts TGF-β1-Induced EMT in Renal Fibrosis". International Journal of Cell Biology 2019 (7 липня 2019): 1–15. http://dx.doi.org/10.1155/2019/9151394.

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Renal tubulointerstitial fibrosis is the final common pathway in end-stage renal disease and is characterized by aberrant accumulation of extracellular matrix (ECM) components secreted by myofibroblasts. Tubular type 2 EMT, induced by TGF-β, plays an important role in renal fibrosis, by participating directly or indirectly in myofibroblasts generation. TGF-β1-induced apoptosis and fibrosis in experimental chronic murine kidney diseases are concomitantly associated with an intrarenal decreased expression of the IL-15 survival factor. Since IL-15 counteracts TGF-β1 effects in different cell mode
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Chonov, Dimitur Chavdarov, Maria Magdalena Krasimirova Ignatova, Julian Rumenov Ananiev, and Maya Vladova Gulubova. "IL-6 Activities in the Tumour Microenvironment. Part 1." Open Access Macedonian Journal of Medical Sciences 7, no. 14 (2019): 2391–98. http://dx.doi.org/10.3889/oamjms.2019.589.

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The predominant role of IL-6 in cancer is its key promotion of tumour growth. IL-6 binds IL-6 receptor (IL-6R) and the membrane-bound glycoprotein gp130. The complex I-6/IL-6R/gp130 starts the Janus kinases (JAKs) and signal transducer and activator of transcription 3 (STAT3) or JAK/STAT3 pathway. IL-6R exits in two forms: a membrane-bound IL-6Rα subunit (mIL-6R) that participates in classic signalling pathway and soluble IL-6R subunit (sIL-6R) engaged in trans-signalling. The pro-tumour functions of IL-6 are associated with STAT3, a major oncogenic transcription factor that triggers up-regula
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Guo, Chao, Yanying Fan, Alexander Aronov та ін. "Abstract 5512: CBLB, CISH and CD70 multiplexed gene knockout with CRISPR/Cas9 enhances cytotoxicity of CD70-CAR NK cells and provides greater resistance to TGF-β for cancer immunotherapy". Cancer Research 82, № 12_Supplement (2022): 5512. http://dx.doi.org/10.1158/1538-7445.am2022-5512.

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Abstract Natural killer (NK) cells provide an attractive platform for development of effective cancer immunotherapies. NK cells are known for their ability to kill tumor cells and do not elicit graft-versus-host disease, making them a potential source of ‘off-the-shelf’ allogeneic cell therapy. NK cells are also amenable to CRISPR genomic engineering to enhance the antitumor activity of NK cells by increasing their cytotoxicity, overcoming suppression within the tumor microenvironment, or promoting their persistence and homing to tumor sites. Cytokine inducible SH2-containing protein (CISH) is
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Liu, Cheng, Xiaorong Chen, Ling Yang, Tatiana Kisseleva, David A. Brenner та Ekihiro Seki. "Transcriptional Repression of the Transforming Growth Factor β (TGF-β) Pseudoreceptor BMP and Activin Membrane-bound Inhibitor (BAMBI) by Nuclear Factor κB (NF-κB) p50 Enhances TGF-β Signaling in Hepatic Stellate Cells". Journal of Biological Chemistry 289, № 10 (2014): 7082–91. http://dx.doi.org/10.1074/jbc.m113.543769.

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Liu, Ning, Toshiaki Makino, Fumiaki Nogaki, et al. "Coagulation in the mesangial area promotes ECM accumulation through factor V expression in MsPGN in rats." American Journal of Physiology-Renal Physiology 287, no. 4 (2004): F612—F620. http://dx.doi.org/10.1152/ajprenal.00322.2003.

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It is well known that tissue factor starts the extrinsic coagulation pathway, which activates factor X to Xa, and factor V is a membrane-bound potent cofactor for the terminating stage of prothrombin activation by factor Xa. In a previous in vitro study, factor V was induced in cultured mesangial cells by inflammatory stimulation and increased expression of factor V promoted fibrin generation on the cultured mesangial cell surface. We report that extracellular matrix (ECM) accumulation is increased in association with coagulation in the mesangial area through factor V expression in mesangiopro
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Chen, Yongyan, Rui Sun, Xunyao Wu, Min Cheng, Haiming Wei та Zhigang Tian. "CD4+CD25+ Regulatory T Cells Inhibit Natural Killer Cell Hepatocytotoxicity of Hepatitis B Virus Transgenic Mice via Membrane-Bound TGF-β and OX40". Journal of Innate Immunity 8, № 1 (2015): 30–42. http://dx.doi.org/10.1159/000431150.

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CD4+CD25+ regulatory T cells (Tregs) are involved in the regulation of physiological and pathological hepatic immune responses, but the roles are not well explored in natural killer (NK) cell-mediated liver diseases. In this study, using the NK cell-mediated oversensitive liver injury model of hepatitis B virus transgenic (HBs-Tg) mice triggered by a low dose of concanavalin A, it was observed that an increased number of CD4+CD25+Foxp3+ Tregs were accumulated in the liver, along with the recovery of liver injury. Adoptive transfer of hepatic Tregs from HBs-Tg mice but not wild B6 mice could si
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Gregg, Randal K., Renu Jain, Scott J. Schoenleber та ін. "A Sudden Decline in Active Membrane-Bound TGF-β Impairs Both T Regulatory Cell Function and Protection against Autoimmune Diabetes". Journal of Immunology 173, № 12 (2004): 7308–16. http://dx.doi.org/10.4049/jimmunol.173.12.7308.

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Brownlie, Demi, Dahlia Doughty-Shenton, Daniel YH Soong та ін. "Metastasis-associated macrophages constrain antitumor capability of natural killer cells in the metastatic site at least partially by membrane bound transforming growth factor β". Journal for ImmunoTherapy of Cancer 9, № 1 (2021): e001740. http://dx.doi.org/10.1136/jitc-2020-001740.

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BackgroundMetastatic breast cancer is a leading cause of cancer-related death in women worldwide. Infusion of natural killer (NK) cells is an emerging immunotherapy for such malignant tumors, although elimination of the immunosuppressive tumor environment is required to improve its efficacy. The effects of this “metastatic” tumor environment on NK cells, however, remain largely unknown. Previous studies, including our own, have demonstrated that metastasis-associated macrophages (MAMs) are one of the most abundant immune cell types in the metastatic tumor niche in mouse models of metastatic br
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Kuhn, Chantal, Rafael Machado Rezende, Hanane M’Hamdi, Andre Pires da Cunha та Howard L. Weiner. "IL-6 Inhibits Upregulation of Membrane-Bound TGF-β 1 on CD4+ T Cells and Blocking IL-6 Enhances Oral Tolerance". Journal of Immunology 198, № 3 (2016): 1202–9. http://dx.doi.org/10.4049/jimmunol.1600921.

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Yang, Zhi-Zhang, Deanna M. Grote, Steven C. Ziesmer та ін. "Soluble and Membrane-Bound TGF-β-Mediated Regulation of Intratumoral T Cell Differentiation and Function in B-Cell Non-Hodgkin Lymphoma". PLoS ONE 8, № 3 (2013): e59456. http://dx.doi.org/10.1371/journal.pone.0059456.

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Villar, Ana V., Raquel García, Miguel Llano та ін. "BAMBI (BMP and activin membrane-bound inhibitor) protects the murine heart from pressure-overload biomechanical stress by restraining TGF-β signaling". Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 1832, № 2 (2013): 323–35. http://dx.doi.org/10.1016/j.bbadis.2012.11.007.

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Hejenkowska, Ewelina D., Hayrettin Yavuz, and Agnieszka Swiatecka-Urban. "Beyond Borders of the Cell: How Extracellular Vesicles Shape COVID-19 for People with Cystic Fibrosis." International Journal of Molecular Sciences 25, no. 7 (2024): 3713. http://dx.doi.org/10.3390/ijms25073713.

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The interaction between extracellular vesicles (EVs) and SARS-CoV-2, the virus causing COVID-19, especially in people with cystic fibrosis (PwCF) is insufficiently studied. EVs are small membrane-bound particles involved in cell–cell communications in different physiological and pathological conditions, including inflammation and infection. The CF airway cells release EVs that differ from those released by healthy cells and may play an intriguing role in regulating the inflammatory response to SARS-CoV-2. On the one hand, EVs may activate neutrophils and exacerbate inflammation. On the other h
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Mesnard, Daniel, and Daniel B. Constam. "Imaging proprotein convertase activities and their regulation in the implanting mouse blastocyst." Journal of Cell Biology 191, no. 1 (2010): 129–39. http://dx.doi.org/10.1083/jcb.201005026.

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Axis formation and allocation of pluripotent progenitor cells to the germ layers are governed by the TGF-β–related Nodal precursor and its secreted proprotein convertases (PCs) Furin and Pace4. However, when and where Furin and Pace4 first become active have not been determined. To study the distribution of PCs, we developed a novel cell surface–targeted fluorescent biosensor (cell surface–linked indicator of proteolysis [CLIP]). Live imaging of CLIP in wild-type and Furin- and Pace4-deficient embryonic stem cells and embryos revealed that Furin and Pace4 are already active at the blastocyst s
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