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Activation of FXR protects against renal fibrosis via suppressing Smad3 expression
Renal fibrosis is the common pathway of most chronic kidney disease progression to end-stage renal failure. The nuclear receptor FXR (farnesoid X receptor), a multiple functional transcription factor, plays an important role in protecting against fibrosis. The TGFβ-Smad signaling has a central role...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5112546/ https://www.ncbi.nlm.nih.gov/pubmed/27853248 http://dx.doi.org/10.1038/srep37234 |
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author | Zhao, Kai He, Jialin Zhang, Yan Xu, Zhizhen Xiong, Haojun Gong, Rujun Li, Song Chen, Shan He, Fengtian |
author_facet | Zhao, Kai He, Jialin Zhang, Yan Xu, Zhizhen Xiong, Haojun Gong, Rujun Li, Song Chen, Shan He, Fengtian |
author_sort | Zhao, Kai |
collection | PubMed |
description | Renal fibrosis is the common pathway of most chronic kidney disease progression to end-stage renal failure. The nuclear receptor FXR (farnesoid X receptor), a multiple functional transcription factor, plays an important role in protecting against fibrosis. The TGFβ-Smad signaling has a central role in kidney fibrosis. However, it remains unclear whether FXR plays direct anti-fibrotic effect in renal fibrosis via regulating TGFβ-Smad pathway. In this study, we found that the level of FXR was negatively correlated with that of Smad3 and fibronectin (a marker of fibrosis) in human fibrotic kidneys. Activation of FXR suppressed kidney fibrosis and downregulated Smad3 expression, which was markedly attenuated by FXR antagonist. Moreover, the FXR-mediated repression of fibrosis was significantly alleviated by ectopic expression of Smad3. Luciferase reporter assay revealed that FXR activation inhibited the transcriptional activity of Smad3 gene promoter. The in vivo experiments showed that FXR agonist protected against renal fibrosis and downregulated Smad3 expression in UUO mice. These results suggested that FXR may serve as an important negative regulator for manipulating Smad3 expression, and the FXR/Smad3 pathway may be a novel target for the treatment of renal fibrosis. |
format | Online Article Text |
id | pubmed-5112546 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-51125462016-11-23 Activation of FXR protects against renal fibrosis via suppressing Smad3 expression Zhao, Kai He, Jialin Zhang, Yan Xu, Zhizhen Xiong, Haojun Gong, Rujun Li, Song Chen, Shan He, Fengtian Sci Rep Article Renal fibrosis is the common pathway of most chronic kidney disease progression to end-stage renal failure. The nuclear receptor FXR (farnesoid X receptor), a multiple functional transcription factor, plays an important role in protecting against fibrosis. The TGFβ-Smad signaling has a central role in kidney fibrosis. However, it remains unclear whether FXR plays direct anti-fibrotic effect in renal fibrosis via regulating TGFβ-Smad pathway. In this study, we found that the level of FXR was negatively correlated with that of Smad3 and fibronectin (a marker of fibrosis) in human fibrotic kidneys. Activation of FXR suppressed kidney fibrosis and downregulated Smad3 expression, which was markedly attenuated by FXR antagonist. Moreover, the FXR-mediated repression of fibrosis was significantly alleviated by ectopic expression of Smad3. Luciferase reporter assay revealed that FXR activation inhibited the transcriptional activity of Smad3 gene promoter. The in vivo experiments showed that FXR agonist protected against renal fibrosis and downregulated Smad3 expression in UUO mice. These results suggested that FXR may serve as an important negative regulator for manipulating Smad3 expression, and the FXR/Smad3 pathway may be a novel target for the treatment of renal fibrosis. Nature Publishing Group 2016-11-17 /pmc/articles/PMC5112546/ /pubmed/27853248 http://dx.doi.org/10.1038/srep37234 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Zhao, Kai He, Jialin Zhang, Yan Xu, Zhizhen Xiong, Haojun Gong, Rujun Li, Song Chen, Shan He, Fengtian Activation of FXR protects against renal fibrosis via suppressing Smad3 expression |
title | Activation of FXR protects against renal fibrosis via suppressing Smad3 expression |
title_full | Activation of FXR protects against renal fibrosis via suppressing Smad3 expression |
title_fullStr | Activation of FXR protects against renal fibrosis via suppressing Smad3 expression |
title_full_unstemmed | Activation of FXR protects against renal fibrosis via suppressing Smad3 expression |
title_short | Activation of FXR protects against renal fibrosis via suppressing Smad3 expression |
title_sort | activation of fxr protects against renal fibrosis via suppressing smad3 expression |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5112546/ https://www.ncbi.nlm.nih.gov/pubmed/27853248 http://dx.doi.org/10.1038/srep37234 |
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