title: Hepatic stellate cell is activated by microRNA-181b via PTEN/Akt pathway.
abstract: Activation of hepatic stellate cells (HSCs) is an essential event in the initiation and progression of liver fibrosis. MicroRNAs have been shown to play a pivotal role in regulating HSC functions such as cell proliferation, differentiation, and apoptosis. Recently, miR-181b has been reported to promote HSCs proliferation by targeting p27. But whether alpha-smooth muscle actin (α-SMA) or collagens could be promoted by miR-181b in activated HSCs is still not clear. Therefore, the understanding of the role of miR-181b in liver fibrosis remains limited. Our results showed that miR-181b expression was increased much higher than miR-181a expression in vitro in transforming growth factor-β1-induced HSC activation as well as in vivo in carbon tetrachloride-induced rat liver fibrosis. Of note, overexpression of miR-181b significantly increased the expressions level of α-SMA and type I collagen, and further promoted HSCs proliferation. Furthermore, phosphatase and tensin homologs deleted on chromosome 10 (PTEN), a negative regulator of PI3K/Akt pathway, were confirmed as a direct target of miR-181b. We demonstrated that miR-181b could suppress PTEN expression and increase Akt phosphorylation in HSCs. Interestingly, the effects of miR-181b on the activation of HSCs were blocked down by Akt inhibitor LY294002. Our results revealed a profibrotic role of miR-181b in HSC activation and demonstrated that miR-181b could activate HSCs, at least in part, via PTEN/Akt pathway.
authors.affiliation: Wenzhou Key Laboratory of Surgery, The First Affiliated Hospital of Wenzhou Medical University, No. 2 Fuxue Lane, Wenzhou, 325000, Zhejiang, People's Republic of China.
authors.forename: Jianjian
authors.initials: J
authors.lastname: Zheng
authors.forename: Cunzao
authors.initials: C
authors.lastname: Wu
authors.forename: Ziqiang
authors.initials: Z
authors.lastname: Xu
authors.forename: Peng
authors.initials: P
authors.lastname: Xia
authors.forename: Peihong
authors.initials: P
authors.lastname: Dong
authors.forename: Bicheng
authors.initials: B
authors.lastname: Chen
authors.forename: Fujun
authors.initials: F
authors.lastname: Yu
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002251:Carbon Tetrachloride; D002460:Cell Line; D002867:Chromones / Q000494:pharmacology; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D000090602:Collagen Type I, alpha 1 Chain; D015870:Gene Expression / Q000187:drug effects; D055166:Hepatic Stellate Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D009025:Morpholines / Q000494:pharmacology; D009130:Muscle, Smooth / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000235:genetics* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology
chemical_list: D020413:3' Untranslated Regions; D000199:Actins; D002251:Carbon Tetrachloride; D002867:Chromones; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D035683:MicroRNAs; D009025:Morpholines; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D053773:Transforming Growth Factor beta1; C540193:MIrn181 microRNA, human; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C494929:PTEN protein, human