Oncotarget

Research Papers:

Cryptotanshinone hinders renal fibrosis and epithelial transdifferentiation in obstructive nephropathy by inhibiting TGF-β1/Smad3/integrin β1 signal

Wei Wang _, Pang-Hu Zhou, Wei Hu, Chang-Geng Xu, Xiang-Jun Zhou, Chao-Zhao Liang and Jie Zhang

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Oncotarget. 2018; 9:26625-26637. https://doi.org/10.18632/oncotarget.23803

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Abstract

Wei Wang1,2,*, Pang-Hu Zhou3,*, Wei Hu4, Chang-Geng Xu5, Xiang-Jun Zhou6, Chao-Zhao Liang1,* and Jie Zhang2,7,*

1Department of Urology, The First Affiliated Hospital of Anhui Medical University and Institute of Urology, Anhui Medical University, Hefei, Anhui, 232200, China

2Department of Urology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, 430060, China

3Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, 430060, China

4Department of Urology, The First Affiliated Hospital of Nan-Hua University, Henyang, Hunan, 421001, China

5Department of Urology, Wuhan Central Hospital, Wuhan, Hubei Province, 430014, China

6Department of Urology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, 430060, China

7Huangshi Central Hospital, Hubei Polytechnic University, Huangshi, Hubei Province, 435000, China

*These authors contributed equally to this work

Correspondence to:

Chao-Zhao Liang, email: [email protected]

Jie Zhang, email: [email protected]

Keywords: cryptotanshinone; kidney fibrosis; epithelial-mesenchymal transition; Smad3; integrin β1

Received: October 02, 2016     Accepted: September 03, 2017     Epub: December 27, 2017     Published: June 01, 2018

ABSTRACT

Recent studies have reported that CTS can alleviate cardiac fibrosis. However, the effects of CTS on kidney fibrosis and EMT are still unknown. This study explored whether CTS could attenuate tubulointerstitial fibrosis as well as EMT, and investigated the potential underlying mechanisms. In this study, an in vivo UUO mouse model and an in vitro TGF-β1 stimulated normal renal tubular kidney epithelial cell model were established. In UUO model, administration of 50 mg kg-1 day-1 CTS markedly decreased the occurrence of kidney injury and the accumulation of fibronectin and collagen-1. In addition, CTS reduced the expression level of α-SMA but retained E-cadherin in obstructed kidneys. In vitro, CTS suppressed the expression of fibronectin, collagen-1 and α-SMA but retained that of E-cadherin. Furthermore, CTS selectively abolished the activation of Smad3 and suppressed the nuclear translocation of Smad2, Smad3 and Smad4. CTS could block the promoter activity of integrin β1 induced by Smad3. Furthermore, CTS inhibited Smad3 binding to integrin β1 promoter sequences. These data suggest that CTS can ameliorate kidney fibrosis and EMT, at least in part, by inhibiting the TGF-β1/Smad3/integrin β1 signaling pathway.


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