title: MicroRNA-21 activates hepatic stellate cells via PTEN/Akt signaling.
abstract: Activation of hepatic stellate cells is the key event in the liver fibrosis. miRs have been shown to play fundamental role in diverse biological and pathological processes. In the present study, we investigated the fibrogenic role of miR-21 in human hepatic stellate LX-2 cells and explored underlying mechanisms. The results showed that treatment of LX-2 cells with platelet-derived growth factor (PDGF)-BB significantly stimulated α1(I) collagen mRNA synthesis and the protein expression of α-SMA, which are characteristics of activation of hepatic stellate cells and simultaneously increased miR-21 expression. Downregulation of miR-21 expression by transfection of anti-miR-21 into LX-2 cells prevented PDGF-BB-induced LX-2 cell activation. Overexpression of miR-21 expression alone also stimulated LX-2 cell activation, while downregulation of miR-21 expression suppressed LX-2 cell activation. miR-21 also played a role in mRNA expression and activity of matrix metalloproteinase 2 (MMP2) in LX-2 cells. Moreover, overexpression of miR-21 decreased protein expression of PTEN in LX-2 cells, resulting in activation of the Akt. Inhibition of Akt signaling by specific inhibitor LY 294002 blocked miR-21-induced fibrogenic effects in LX-2 cells. In summary, miR-21 is an important mediator in LX-2 cell activation. The fibrogenic effects of miR-21 on LX-2 cell activation are mediated through PTEN/Akt pathway. miR-21 may be a potential novel molecular target for the liver fibrosis.
authors: Department of Gastroenterology, Jinshan Hospital of Fudan University, 201508 Shanghai, China.
authors: Jun
authors: J
authors: Wei
authors: Lisha
authors: L
authors: Feng
authors: Zhong
authors: Z
authors: Li
authors: Guoxiong
authors: G
authors: Xu
authors: Xiaoming
authors: X
authors: Fan
mesh_terms: D000077214:Becaplermin; D002460:Cell Line; D002867:Chromones / Q000494:pharmacology; D024042:Collagen Type I / Q000235:genetics; D015536:Down-Regulation; D005786:Gene Expression Regulation; D055166:Hepatic Stellate Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008103:Liver Cirrhosis / Q000473:pathology; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009025:Morpholines / Q000494:pharmacology; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D020574:Proto-Oncogene Proteins c-sis / Q000008:administration & dosage / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D002867:Chromones; D024042:Collagen Type I; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D009025:Morpholines; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; D000077214:Becaplermin; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2