caa a22 4500 606234942 CHVBK 20210128101240.0 cr unu---uuuuu 210128e20150101xx s 000 0 eng 10.1007/s11010-014-2199-8 doi (NATIONALLICENCE)springer-10.1007/s11010-014-2199-8 Hepatic stellate cell is activated by microRNA-181b via PTEN/Akt pathway [Elektronische Daten] [Jianjian Zheng, Cunzao Wu, Ziqiang Xu, Peng Xia, Peihong Dong, Bicheng Chen, Fujun Yu] 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. Springer Science+Business Media New York, 2014 microRNA-181b nationallicence Hepatic stellate cells nationallicence PTEN nationallicence TGF-β1 nationallicence PTEN : Phosphatase and tensin homolog deleted on chromosome 10 nationallicence HSCs : Hepatic stellate cells nationallicence miRNAs : MicroRNAs nationallicence ECM : Extracellular matrix nationallicence α-SMA : Alpha-smooth muscle actin nationallicence TGF-β1 : Transforming growth factor-β1 nationallicence 3′-UTR : 3′-Untranslated region nationallicence CCl4 : Carbon tetrachloride nationallicence Col1A1 : Alpha-1(I) collagen nationallicence Zheng Jianjian Wenzhou Key Laboratory of Surgery, The First Affiliated Hospital of Wenzhou Medical University, No. 2 Fuxue Lane, 325000, Wenzhou, Zhejiang, People's Republic of China aut Wu Cunzao Institute of Organ Transplantation, The First Affiliated Hospital of Wenzhou Medical University, 325000, Wenzhou, Zhejiang, People's Republic of China aut Xu Ziqiang Institute of Organ Transplantation, The First Affiliated Hospital of Wenzhou Medical University, 325000, Wenzhou, Zhejiang, People's Republic of China aut Xia Peng Institute of Organ Transplantation, The First Affiliated Hospital of Wenzhou Medical University, 325000, Wenzhou, Zhejiang, People's Republic of China aut Dong Peihong Department of Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical University, No. 2 Fuxue Lane, 325000, Wenzhou, Zhejiang, People's Republic of China aut Chen Bicheng Wenzhou Key Laboratory of Surgery, The First Affiliated Hospital of Wenzhou Medical University, No. 2 Fuxue Lane, 325000, Wenzhou, Zhejiang, People's Republic of China aut Yu Fujun Department of Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical University, No. 2 Fuxue Lane, 325000, Wenzhou, Zhejiang, People's Republic of China aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 398/1-2(2015-01-01), 1-9 0300-8177 398:1-2<1 2015 398 11010 https://doi.org/10.1007/s11010-014-2199-8 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-014-2199-8 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Zheng Jianjian Wenzhou Key Laboratory of Surgery, The First Affiliated Hospital of Wenzhou Medical University, No. 2 Fuxue Lane, 325000, Wenzhou, Zhejiang, People's Republic of China aut NATIONALLICENCE 700 1- Wu Cunzao Institute of Organ Transplantation, The First Affiliated Hospital of Wenzhou Medical University, 325000, Wenzhou, Zhejiang, People's Republic of China aut NATIONALLICENCE 700 1- Xu Ziqiang Institute of Organ Transplantation, The First Affiliated Hospital of Wenzhou Medical University, 325000, Wenzhou, Zhejiang, People's Republic of China aut NATIONALLICENCE 700 1- Xia Peng Institute of Organ Transplantation, The First Affiliated Hospital of Wenzhou Medical University, 325000, Wenzhou, Zhejiang, People's Republic of China aut NATIONALLICENCE 700 1- Dong Peihong Department of Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical University, No. 2 Fuxue Lane, 325000, Wenzhou, Zhejiang, People's Republic of China aut NATIONALLICENCE 700 1- Chen Bicheng Wenzhou Key Laboratory of Surgery, The First Affiliated Hospital of Wenzhou Medical University, No. 2 Fuxue Lane, 325000, Wenzhou, Zhejiang, People's Republic of China aut NATIONALLICENCE 700 1- Yu Fujun Department of Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical University, No. 2 Fuxue Lane, 325000, Wenzhou, Zhejiang, People's Republic of China aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 398/1-2(2015-01-01), 1-9 0300-8177 398:1-2<1 2015 398 11010