title: MircoRNA-145 promotes activation of hepatic stellate cells via targeting krüppel-like factor 4.
abstract: 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.
authors.affiliation: Division of Gastroenterology &Hepatology, West China Hospital, Sichuan University, Chengdu 610041, China.|Department of Biostatistics, JC school of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, China.
authors.forename: Ruoting
authors.initials: R
authors.lastname: Men
authors.affiliation: Division of Gastroenterology &Hepatology, West China Hospital, Sichuan University, Chengdu 610041, China.
authors.forename: Maoyao
authors.initials: M
authors.lastname: Wen
authors.affiliation: Laboratory of Cardiovascular Diseases, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu 610041, China.
authors.forename: Mingyue
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Division of Gastroenterology &Hepatology, West China Hospital, Sichuan University, Chengdu 610041, China.
authors.forename: Xuelian
authors.initials: X
authors.lastname: Dan
authors.affiliation: Creation and Management of a Tumour Bank, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: Zongze
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Laboratory of Cardiovascular Diseases, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu 610041, China.
authors.forename: Wenchao
authors.initials: W
authors.lastname: Wu
authors.affiliation: Department of Biostatistics, JC school of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, China.
authors.forename: Maggie Haitian
authors.initials: MH
authors.lastname: Wang
authors.affiliation: Laboratory of Cardiovascular Diseases, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu 610041, China.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Liu
authors.affiliation: Division of Gastroenterology &Hepatology, West China Hospital, Sichuan University, Chengdu 610041, China.
authors.forename: Li
authors.initials: L
authors.lastname: Yang
mesh_terms: D000818:Animals; D015536:Down-Regulation / Q000187:drug effects; D055785:Gene Knockdown Techniques; D055166:Hepatic Stellate Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism*; D008103:Liver Cirrhosis / Q000235:genetics / Q000473:pathology; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; C000715469:Klf4 protein, rat; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; C541010:MIRN145 microRNA, human; C543499:MIRN145a microRNA, mouse; D035683:MicroRNAs; D016212:Transforming Growth Factor beta