Document Detail


Resveratrol Inhibits Epithelial-Mesenchymal Transition and Renal Fibrosis by Antagonizing the Hedgehog Signaling Pathway.
MedLine Citation:
PMID:  25219324     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Epithelial-to-mesenchymal transition (EMT), a biologic process in which tubular cells lose their epithelial phenotypes and acquire new characteristic features of mesenchymal properties, is increasingly recognized as an integral part of renal tissue fibrogenesis. Recent studies indicate that resveratrol, a botanical compound derived mainly from the skins of red grapes, may have anti-fibrotic effects in many tissues, but the potential molecular mechanism remains unknown. In the present study, we identified that resveratrol inhibits the induction of EMT and deposition of extracellular matrix (ECM) through antagonizing the hedgehog pathway in vitro and in vivo. In rats with unilateral ureteral obstruction (UUO), administration of resveratrol (20mg/kg/day) significantly reduced serum creatinine. Resveratrol also decreased expression of TGF-β1, and inhibited the phenotypic transition from epithelial cells to mesenchymal cells, and the deposition of ECM in UUO rats. In cultured renal tubular epithelial cells (NRK-52E), TGF-β1-induced EMT and ECM synthesis was abolished with the treatment of resveratrol. The induction of EMT was associated with the activation of the hedgehog pathway. Resveratrol treatment markedly inhibited the over-activity of the hedgehog pathway in the obstructed kidney and in TGF-β1-treated NRK-52E cells, resulted in reduction of cellular proliferation, EMT and ECM accumulation. Thus, these results suggest that resveratrol is able to inhibit EMT and fibrosis in vivo and in vitro through antagonizing the hedgehog pathway, and resveratrol may have therapeutic potential for patients with fibrotic kidney diseases.
Authors:
Yongheng Bai; Hong Lu; Cunzao Wu; Yong Liang; Silu Wang; Chengcheng Lin; Bicheng Chen; Peng Xia
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-9-11
Journal Detail:
Title:  Biochemical pharmacology     Volume:  -     ISSN:  1873-2968     ISO Abbreviation:  Biochem. Pharmacol.     Publication Date:  2014 Sep 
Date Detail:
Created Date:  2014-9-15     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0101032     Medline TA:  Biochem Pharmacol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2014. Published by Elsevier Inc.
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