Open AccessMircoRNA-145 promotes activation of hepatic stellate cells via targeting krüppel-like factor 4
Author(s) -
Ruoting Men,
Maoyao Wen,
Mingyue Zhao,
Xuelian Dan,
Zhen Yang,
Wenchao Wu,
Maggie Wang,
Xiaojing Liu,
Yang Li
Publication year - 2017
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/srep40468
Subject(s) - klf4 , hepatic stellate cell , small hairpin rna , krüppel , sma* , cancer research , microbiology and biotechnology , hepatic fibrosis , chemistry , biology , fibrosis , gene expression , medicine , endocrinology , gene knockdown , transcription factor , gene , sox2 , biochemistry , mathematics , combinatorics
Krüppel-like Factor 4 (KLF4), a target gene of miR-145, can negatively regulate lung fibrosis. However, the potential role of KLF4 and miR-145 in hepatic stellate cells (HSCs) activation or in hepatic fibrosis keeps unclear. This study aims to characterize miR-145 and KLF4 in activated HSCs and liver cirrhotic, and the underlying molecular basis. miR-145 was significantly up-regulated, while KLF4 was dramatically down-regulated during the activation of rat primary HSCs and TGF-βtreated HSCs. Furthermore, miR-145 mimics induced and inhibition of miR-145 reduced α-SMA and COL-I expression in primary HSCs. Additionally, the mRNA and protein levels of KLF4 in the liver of cirrhotic patients and rats were significantly down-regulated. α-SMA and COL-I were increased after inhibition of KLF4 by specific shRNA in primary HSCs. Forced KLF4 expression led to a reduction of α-SMA and COL-I expression in HSCs. miR-145 promotes HSC activation and liver fibrosis by targeting KLF4.