Hepatic stellate cell is activated by microRNA-181b via PTEN/Akt pathway

• Published in: Molecular and cellular biochemistry Vol. 398; no. 1-2; pp. 1 - 9
• Main Authors: Zheng, Jianjian, Wu, Cunzao, Xu, Ziqiang, Xia, Peng, Dong, Peihong, Chen, Bicheng, Yu, Fujun
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.01.2015; Springer; Springer Nature B.V
• Subjects: 3' Untranslated Regions - genetics; Actins - genetics; Actins - metabolism; Animals; Biochemistry; Biomedical and Life Sciences; Blotting, Western; Bone morphogenetic proteins; Carbon Tetrachloride; Cardiology; Cell Line; Cells; Chromones - pharmacology; Collagen; Collagen Type I - genetics; Collagen Type I - metabolism; Gene Expression - drug effects; Hepatic Stellate Cells - drug effects; Hepatic Stellate Cells - metabolism; Hepatology; Humans; Life Sciences; Liver Cirrhosis - chemically induced; Liver Cirrhosis - genetics; Liver Cirrhosis - metabolism; Liver diseases; Male; Medical Biochemistry; MicroRNA; MicroRNAs - genetics; Morpholines - pharmacology; Muscle proteins; Muscle, Smooth - metabolism; Oncology; Phosphatidylinositol 3-Kinases - antagonists & inhibitors; Phosphatidylinositol 3-Kinases - metabolism; Phosphorylation - drug effects; Proto-Oncogene Proteins c-akt - metabolism; PTEN Phosphohydrolase - genetics; PTEN Phosphohydrolase - metabolism; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; Ribonucleic acid; RNA; Signal Transduction - drug effects; Transforming Growth Factor beta1 - pharmacology; Transforming growth factors; PTEN; Hepatic stellate cells; TGF-β1; microRNA-181b
• ISSN: 0300-8177; 1573-4919; 1573-4919
• DOI: 10.1007/s11010-014-2199-8

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.