title: MicroRNA-17-5p-activated Wnt/β-catenin pathway contributes to the progression of liver fibrosis.
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 I collagen 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.
authors.affiliation: Department of Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
authors.forename: Fujun
authors.initials: F
authors.lastname: Yu
authors.affiliation: Emergency Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
authors.forename: Zhongqiu
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Department of Pathology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
authors.forename: Kate
authors.initials: K
authors.lastname: Huang
authors.affiliation: Department of Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Wang
authors.affiliation: Institute of Organ Transplantation, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
authors.forename: Ziqiang
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Key Laboratory of Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
authors.forename: Bicheng
authors.initials: B
authors.lastname: Chen
authors.affiliation: Department of Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
authors.forename: Peihong
authors.initials: P
authors.lastname: Dong
authors.affiliation: Key Laboratory of Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
authors.forename: Jianjian
authors.initials: J
authors.lastname: Zheng
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D001572:Benzofurans / Q000494:pharmacology; D015153:Blotting, Western; D002251:Carbon Tetrachloride; D002460:Cell Line; D002478:Cells, Cultured; D018450:Disease Progression; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D055166:Hepatic Stellate Cells / Q000187:drug effects / Q000378:metabolism; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000235:genetics* / Q000517:prevention & control; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008856:Microscopy, Fluorescence; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D060449:Wnt Signaling Pathway / Q000235:genetics*; D053630:Depsides
chemical_list: D020413:3' Untranslated Regions; D001572:Benzofurans; D002251:Carbon Tetrachloride; D004365:Drugs, Chinese Herbal; D016326:Extracellular Matrix Proteins; D036341:Intercellular Signaling Peptides and Proteins; D035683:MicroRNAs; C000601368:MIRN17 microRNA, rat; C521045:Wif1 protein, rat; C076944:salvianolic acid B; D053630:Depsides
keywords: Pathology Section; Salvianolic acid B; Wnt inhibitory factor 1 (WIF1); Wnt/β-catenin pathway; hepatic stellate cells; microRNA-17-5p