Resveratrol inhibits epithelial-mesenchymal transition and renal fibrosis by antagonizing the hedgehog signaling pathway

doi:10.1016/j.bcp.2014.09.002

科研成果详情

题名	Resveratrol inhibits epithelial-mesenchymal transition and renal fibrosis by antagonizing the hedgehog signaling pathway
作者	Bai, Yongheng 1; Lu, Hong2; Wu, Cunzao 3; Liang, Yong1; Wang, Silu1; Lin, Chengcheng 1; Chen, Bicheng 1; Xia, Peng3
发表日期	2014-12-01
发表期刊	BIOCHEMICAL PHARMACOLOGY 影响因子和分区
语种	英语
原始文献类型	Article
关键词	Resveratrol Epithelial-to-mesenchymal transition (EMT) Renal fibrosis Hedgehog signaling pathway
其他关键词	SARMENTOSUM BUNGE EXTRACT ; SONIC HEDGEHOG ; KIDNEY ; CELLS ; ACTIVATION ; MECHANISM ; AKT
摘要	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 (20 mg/kg/day) significantly reduced serum creatinine. Resveratrol also decreased expression of TGF-beta 1, 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-beta 1 -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-beta 1-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. (C) 2014 Elsevier Inc. All rights reserved.
资助项目	Zhejiang Extremely Key Subject of Surgery; Wenzhou Municipal Science and Technology Plan Project [Y20110028, Y20130158]; Natural Science Foundation of Zhejiang province, ChinaNatural Science Foundation of Zhejiang Province [LQ12H05001, LY12H05004]
出版者	PERGAMON-ELSEVIER SCIENCE LTD
出版地	OXFORD
ISSN	0006-2952
EISSN	1873-2968
卷号	92 期号:3 页码:484-493
DOI	10.1016/j.bcp.2014.09.002
页数	10
WOS类目	Pharmacology & Pharmacy
WOS研究方向	Pharmacology & Pharmacy
WOS记录号	WOS:000345955400009
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	25219324
SCOPUSEID	2-s2.0-84910634437
通讯作者地址	[Xia, Peng]Department of Transplantation,Wenzhou Medical University,2# Fuxue Lane,Wenzhou,325000,China
Scopus学科分类	Biochemistry;Pharmacology
引用统计	被引频次：50[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/14567
专题	检验医学院（生命科学学院、生物学实验教学中心）附属第一医院_移植科
通讯作者	Xia, Peng
作者单位	1.Wenzhou Key Laboratory of Surgery,Wenzhou Medical University,Wenzhou,China; 2.Department of Laboratory Medicine,Wenzhou Medical University,Wenzhou,China; 3.Department of Transplantation,Wenzhou Medical University,2# Fuxue Lane,Wenzhou,325000,China
第一作者单位	温州医科大学
通讯作者单位	温州医科大学
第一作者的第一单位	温州医科大学
推荐引用方式 GB/T 7714	Bai, Yongheng,Lu, Hong,Wu, Cunzao,et al. Resveratrol inhibits epithelial-mesenchymal transition and renal fibrosis by antagonizing the hedgehog signaling pathway[J]. BIOCHEMICAL PHARMACOLOGY,2014,92(3):484-493.
APA	Bai, Yongheng., Lu, Hong., Wu, Cunzao., Liang, Yong., Wang, Silu., ... & Xia, Peng. (2014). Resveratrol inhibits epithelial-mesenchymal transition and renal fibrosis by antagonizing the hedgehog signaling pathway. BIOCHEMICAL PHARMACOLOGY, 92(3), 484-493.
MLA	Bai, Yongheng,et al."Resveratrol inhibits epithelial-mesenchymal transition and renal fibrosis by antagonizing the hedgehog signaling pathway".BIOCHEMICAL PHARMACOLOGY 92.3(2014):484-493.