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Lovastatin Alleviates Endothelial-to-Mesenchymal Transition in Glomeruli via Suppression of Oxidative Stress and TGF-β1 Signaling

Statins may decrease chronic kidney diseases (CKDs) risk, but their underlying molecular mechanisms are not completely understood. Recent studies indicate Endothelial-to-mesenchymal transition (EndMT) plays an important role contributing to renal interstitial fibrosis. In the present study, we first...

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Autores principales: Ma, Zejun, Zhu, Lili, Liu, Yan, Wang, Zhida, Yang, Yang, Chen, Liming, Lu, Qiulun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5513942/
https://www.ncbi.nlm.nih.gov/pubmed/28769803
http://dx.doi.org/10.3389/fphar.2017.00473
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author Ma, Zejun
Zhu, Lili
Liu, Yan
Wang, Zhida
Yang, Yang
Chen, Liming
Lu, Qiulun
author_facet Ma, Zejun
Zhu, Lili
Liu, Yan
Wang, Zhida
Yang, Yang
Chen, Liming
Lu, Qiulun
author_sort Ma, Zejun
collection PubMed
description Statins may decrease chronic kidney diseases (CKDs) risk, but their underlying molecular mechanisms are not completely understood. Recent studies indicate Endothelial-to-mesenchymal transition (EndMT) plays an important role contributing to renal interstitial fibrosis. In the present study, we first investigated whether lovastatin could ameliorate renal fibrosis via suppression of EndMT and its possible mechanism. In vitro experiments, lovastatin significantly ameliorated microalbuminuria and pathologic changes in diabetic rats. Double labeling immunofluorescence showed lovastatin could inhibit EndMT in glomeruli. Furthermore, lovastatin could inhibit oxidative stress and down-regulate TGF-β1-Smad signaling. Consistent alterations were observed in vivo that lovastatin substantially suppressed EndMT and TGF-β1 signaling induced by high glucose in glomerular endothelial cells (GEnCs). These data indicated that lovastatin could ameliorate EndMT in glomeruli in diabetic nephropathy, the mechanism of which might be at least partly through suppression of oxidative stress and TGF-β1/Smad signaling pathway.
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spelling pubmed-55139422017-08-02 Lovastatin Alleviates Endothelial-to-Mesenchymal Transition in Glomeruli via Suppression of Oxidative Stress and TGF-β1 Signaling Ma, Zejun Zhu, Lili Liu, Yan Wang, Zhida Yang, Yang Chen, Liming Lu, Qiulun Front Pharmacol Pharmacology Statins may decrease chronic kidney diseases (CKDs) risk, but their underlying molecular mechanisms are not completely understood. Recent studies indicate Endothelial-to-mesenchymal transition (EndMT) plays an important role contributing to renal interstitial fibrosis. In the present study, we first investigated whether lovastatin could ameliorate renal fibrosis via suppression of EndMT and its possible mechanism. In vitro experiments, lovastatin significantly ameliorated microalbuminuria and pathologic changes in diabetic rats. Double labeling immunofluorescence showed lovastatin could inhibit EndMT in glomeruli. Furthermore, lovastatin could inhibit oxidative stress and down-regulate TGF-β1-Smad signaling. Consistent alterations were observed in vivo that lovastatin substantially suppressed EndMT and TGF-β1 signaling induced by high glucose in glomerular endothelial cells (GEnCs). These data indicated that lovastatin could ameliorate EndMT in glomeruli in diabetic nephropathy, the mechanism of which might be at least partly through suppression of oxidative stress and TGF-β1/Smad signaling pathway. Frontiers Media S.A. 2017-07-18 /pmc/articles/PMC5513942/ /pubmed/28769803 http://dx.doi.org/10.3389/fphar.2017.00473 Text en Copyright © 2017 Ma, Zhu, Liu, Wang, Yang, Chen and Lu. 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.
spellingShingle Pharmacology
Ma, Zejun
Zhu, Lili
Liu, Yan
Wang, Zhida
Yang, Yang
Chen, Liming
Lu, Qiulun
Lovastatin Alleviates Endothelial-to-Mesenchymal Transition in Glomeruli via Suppression of Oxidative Stress and TGF-β1 Signaling
title Lovastatin Alleviates Endothelial-to-Mesenchymal Transition in Glomeruli via Suppression of Oxidative Stress and TGF-β1 Signaling
title_full Lovastatin Alleviates Endothelial-to-Mesenchymal Transition in Glomeruli via Suppression of Oxidative Stress and TGF-β1 Signaling
title_fullStr Lovastatin Alleviates Endothelial-to-Mesenchymal Transition in Glomeruli via Suppression of Oxidative Stress and TGF-β1 Signaling
title_full_unstemmed Lovastatin Alleviates Endothelial-to-Mesenchymal Transition in Glomeruli via Suppression of Oxidative Stress and TGF-β1 Signaling
title_short Lovastatin Alleviates Endothelial-to-Mesenchymal Transition in Glomeruli via Suppression of Oxidative Stress and TGF-β1 Signaling
title_sort lovastatin alleviates endothelial-to-mesenchymal transition in glomeruli via suppression of oxidative stress and tgf-β1 signaling
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5513942/
https://www.ncbi.nlm.nih.gov/pubmed/28769803
http://dx.doi.org/10.3389/fphar.2017.00473
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