Oncotarget

Research Papers: Pathology:

MicroRNA-17-5p-activated Wnt/β-catenin pathway contributes to the progression of liver fibrosis

Fujun Yu, Zhongqiu Lu, Kate Huang, Xiaodong Wang, Ziqiang Xu, Bicheng Chen, Peihong Dong and Jianjian Zheng _

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Oncotarget. 2016; 7:81-93. https://doi.org/10.18632/oncotarget.6447

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Abstract

Fujun Yu1,*, Zhongqiu Lu2,*, Kate Huang3, Xiaodong Wang1, Ziqiang Xu4, Bicheng Chen5, Peihong Dong1 and Jianjian Zheng5

1 Department of Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China

2 Emergency Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China

3 Department of Pathology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China

4 Institute of Organ Transplantation, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China

5 Key Laboratory of Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China

* These authors have contributed equally to this work

Correspondence to:

Jianjian Zheng, email:

Peihong Dong, email:

Keywords: microRNA-17-5p, Wnt/β-catenin pathway, hepatic stellate cells, Salvianolic acid B, Wnt inhibitory factor 1 (WIF1), Pathology Section

Received: July 09, 2015 Accepted: November 22, 2015 Published: December 02, 2015

Abstract

Aberrant Wnt/β-catenin pathway contributes to the development of liver fibrosis. MicroRNAs (MiRNAs) are found to act as regulators of the activation of hepatic stellate cell (HSC) in liver fibrosis. However, whether miRNAs activate Wnt/β-catenin pathway in activated HSCs during liver fibrosis is largely unknown. In this study, we found that Salvianolic acid B (Sal B) treatment significantly inhibited liver fibrosis in CCl4-treated rats, HSC-T6 cells and rat primary HSCs, resulting in the suppression of type Ⅰcollagen and alpha-smooth muscle actin. Also, Sal B suppressed HSC activation and cell proliferation in vitro. Interestingly, Sal B treatment induced the inactivation of Wnt/β-catenin pathway, with an increase in P-β-catenin and Wnt inhibitory factor 1 (WIF1). We demonstrated that the anti-fibrotic effects caused by Sal B were, at least in part, via WIF1. Moreover, our study revealed that miR-17-5p was reduced in vivo and in vitro after Sal B treatment. As confirmed by luciferase activity assays, WIF1 was a direct target of miR-17-5p. Notably, the suppression of HSCs induced by Sal B was almost inhibited by miR-17-5p mimics. Collectively, we demonstrated that miR-17-5p activates Wnt/β-catenin pathway to result in HSC activation through inhibiting WIF1 expression.


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