TGF-β/Smad signaling in renal fibrosis
TGF-β (transforming growth factor-β) is well identified as a central mediator in renal fibrosis. TGF-β initiates canonical and non-canonical pathways to exert multiple biological effects. Among them, Smad signaling is recognized as a major pathway of TGF-β signaling in progressive renal fibrosis. Du...
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Frontiers Media S.A.
2015
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4365692/ |
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pubmed-43656922015-04-07 TGF-β/Smad signaling in renal fibrosis Meng, Xiao-Ming Tang, Patrick Ming-Kuen Li, Jun Lan, Hui Yao Physiology TGF-β (transforming growth factor-β) is well identified as a central mediator in renal fibrosis. TGF-β initiates canonical and non-canonical pathways to exert multiple biological effects. Among them, Smad signaling is recognized as a major pathway of TGF-β signaling in progressive renal fibrosis. During fibrogenesis, Smad3 is highly activated, which is associated with the down-regulation of an inhibitory Smad7 via an ubiquitin E3-ligases-dependent degradation mechanism. The equilibrium shift between Smad3 and Smad7 leads to accumulation and activation of myofibroblasts, overproduction of ECM (extracellular matrix), and reduction in ECM degradation in the diseased kidney. Therefore, overexpression of Smad7 has been shown to be a therapeutic agent for renal fibrosis in various models of kidney diseases. In contrast, another downstream effecter of TGF-β/Smad signaling pathway, Smad2, exerts its renal protective role by counter-regulating the Smad3. Furthermore, recent studies demonstrated that Smad3 mediates renal fibrosis by down-regulating miR-29 and miR-200 but up-regulating miR-21 and miR-192. Thus, overexpression of miR-29 and miR-200 or down-regulation of miR-21 and miR-192 is capable of attenuating Smad3-mediated renal fibrosis in various mouse models of chronic kidney diseases (CKD). Taken together, TGF-β/Smad signaling plays an important role in renal fibrosis. Targeting TGF-β/Smad3 signaling may represent a specific and effective therapy for CKD associated with renal fibrosis. Frontiers Media S.A. 2015-03-19 /pmc/articles/PMC4365692/ /pubmed/25852569 http://dx.doi.org/10.3389/fphys.2015.00082 Text en Copyright © 2015 Meng, Tang, Li and Lan. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Meng, Xiao-Ming Tang, Patrick Ming-Kuen Li, Jun Lan, Hui Yao |
| spellingShingle |
Meng, Xiao-Ming Tang, Patrick Ming-Kuen Li, Jun Lan, Hui Yao TGF-β/Smad signaling in renal fibrosis |
| author_facet |
Meng, Xiao-Ming Tang, Patrick Ming-Kuen Li, Jun Lan, Hui Yao |
| author_sort |
Meng, Xiao-Ming |
| title |
TGF-β/Smad signaling in renal fibrosis |
| title_short |
TGF-β/Smad signaling in renal fibrosis |
| title_full |
TGF-β/Smad signaling in renal fibrosis |
| title_fullStr |
TGF-β/Smad signaling in renal fibrosis |
| title_full_unstemmed |
TGF-β/Smad signaling in renal fibrosis |
| title_sort |
tgf-β/smad signaling in renal fibrosis |
| description |
TGF-β (transforming growth factor-β) is well identified as a central mediator in renal fibrosis. TGF-β initiates canonical and non-canonical pathways to exert multiple biological effects. Among them, Smad signaling is recognized as a major pathway of TGF-β signaling in progressive renal fibrosis. During fibrogenesis, Smad3 is highly activated, which is associated with the down-regulation of an inhibitory Smad7 via an ubiquitin E3-ligases-dependent degradation mechanism. The equilibrium shift between Smad3 and Smad7 leads to accumulation and activation of myofibroblasts, overproduction of ECM (extracellular matrix), and reduction in ECM degradation in the diseased kidney. Therefore, overexpression of Smad7 has been shown to be a therapeutic agent for renal fibrosis in various models of kidney diseases. In contrast, another downstream effecter of TGF-β/Smad signaling pathway, Smad2, exerts its renal protective role by counter-regulating the Smad3. Furthermore, recent studies demonstrated that Smad3 mediates renal fibrosis by down-regulating miR-29 and miR-200 but up-regulating miR-21 and miR-192. Thus, overexpression of miR-29 and miR-200 or down-regulation of miR-21 and miR-192 is capable of attenuating Smad3-mediated renal fibrosis in various mouse models of chronic kidney diseases (CKD). Taken together, TGF-β/Smad signaling plays an important role in renal fibrosis. Targeting TGF-β/Smad3 signaling may represent a specific and effective therapy for CKD associated with renal fibrosis. |
| publisher |
Frontiers Media S.A. |
| publishDate |
2015 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4365692/ |
| _version_ |
1613200772864933888 |