Kruppel-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-beta treated HSCs. Furthermore, miR-145 mimics induced and inhibition of miR-145 reduced a-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. alpha-SMA and COL-I were increased after inhibition of KLF4 by specific shRNA in primary HSCs. Forced KLF4 expression led to a reduction of a-SMA and COL-I expression in HSCs. miR-145 promotes HSC activation and liver fibrosis by targeting KLF4.

Citation： Men Ruoting, Wen Maoyao, Zhao Mingyue, Dan Xuelian, Yang Zongze, Wu Wenchao, Wang Maggie Haitian, Liu Xiaojing, Yang Li. MircoRNA-145 promotes activation of hepatic stellate cells via targeting kruppel-like factor 4. West China medical Virtual Journal, 2000, 1(1): -. doi: 10.1038/srep40468 Copy