title: MicroRNA-146b regulates hepatic stellate cell activation via targeting of KLF4.
abstract: Background. We previously identified miR-146b as being up-regulated during the development of hepatic fibrosis using deep sequencing technology and gene expression analysis. However, the roles and related mechanisms of miR-146b in hepatic stellate cells (HSCs), which are involved in fibrogenesis and fibrosis, have not been elucidated.
  
  
  RESULTS
  We report that miR-146b expression was increased in TGF-ß1-treated HSCs. TGF- ß1 enhanced α-SMA and COL1A1 protein expression in HSCs and stimulated proliferation of these cells compared with cells transfected with inhibitor NC. Conversely, miR-146b knock-down decreased α-SMA and COL1A1 expression and inhibited HSC proliferation. In addition, we found that miR-146b specifically regulated the translation of Krüppel-like factor 4 (KLF4) by targeting its 3' untranslated region. Forced expression of KLF4 inhibited TGF- ß1-induced enhancement of α-SMA and COL1A1 expression in HSCs, as well as proliferation of these cells. Moreover, miR-146b expression was negatively associated with KLF4 expression but positively associated with expression of α-SMA and COL1A1 during hepatic fibrosis.
  
  
  CONCLUSIONS
  Our findings demonstrate the participation of miR-146b as a novel upstream effector of HSC activation via direct targeting of KLF4. Thus, targeted transfer of miR-146b into HSCs could be a useful strategy for the treatment of hepatic fibrosis.
authors.affiliation: Department of Infectious Disease, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
authors.forename: Shanfei
authors.initials: S
authors.lastname: Ge
authors.affiliation: Department of Infectious Disease, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
authors.forename: Lunli
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Infectious Disease, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Xie
authors.affiliation: Department of Infectious Disease, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Liu
authors.affiliation: Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
authors.forename: Jinni
authors.initials: J
authors.lastname: He
authors.affiliation: Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
authors.forename: Jinwen
authors.initials: J
authors.lastname: He
authors.affiliation: BGI-tianjin, Tianjin, China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Infectious Disease, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
authors.forename: Tianxing
authors.initials: T
authors.lastname: Xiang
mesh_terms: D020413:3' Untranslated Regions; D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D049109:Cell Proliferation; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D000090602:Collagen Type I, alpha 1 Chain; D005786:Gene Expression Regulation; D055166:Hepatic Stellate Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D008106:Liver Cirrhosis, Experimental / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology
chemical_list: D020413:3' Untranslated Regions; D000199:Actins; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D035683:MicroRNAs; D053773:Transforming Growth Factor beta1; C000715469:Klf4 protein, rat; C554180:MIRN146 microRNA, rat; C498862:Acta2 protein, rat