title: microRNA-21 mediates epithelial-mesenchymal transition of human hepatocytes via PTEN/Akt pathway.
abstract: miR-21 has been shown to play fundamental role in diverse biological and pathological processes, including fibrotic diseases. In the present study, we investigated whether miR-21 regulated the fibrogenic epithelial-mesenchymal transition (EMT) in human hepatocytes QSG-7701 and explored underlying mechanisms. The results showed that treatment of QSG-7701 cells with pro-fibrogenic factor TGF-β1 resulted in increased expression of miR-21 and promoted fibrogenic EMT in hepatocytes. Downregulation of miR-21 expression by transfection of anti-miR-21 into QSG-7701 cells inhibited fibrogenic EMT induced by TGF-β1. Furthermore, overexpression of miR-21 alone also resulted in EMT-like transformation in QSG-7701 cells. TGF-β1 treatment resulted in decreased PTEN and increased Akt phosphorylation and anti-miR-21 abolished this effect. Overexpression of miR-21 in QSG-7701 cells also downregulated PTEN and upregulated Akt phosphralation. Inhibition of Akt signaling by specific inhibitor Akt inhibitor IV blocked TGF-β1 and miR-21-induced fibrogenic EMT. In summary, our results identify miR-21 as a key regulator of fibrogenic EMT in hepatocytes via PTEN/Akt pathway. Targeting miR-21 may provide a new therapeutic strategy against hepatic fibrosis.
authors: Department of Gastroenterology, Jinshan Hospital of Fudan University, Shanghai 201508, China.
authors: Zhenyu
authors: Z
authors: Liu
authors: Department of Gastroenterology, Jinshan Hospital of Fudan University, Shanghai 201508, China.
authors: Jingjie
authors: J
authors: Wang
authors: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
authors: Chuanyong
authors: C
authors: Guo
authors: Department of Gastroenterology, Jinshan Hospital of Fudan University, Shanghai 201508, China; Department of Internal Medicine, Shanghai Medical College, Fudan University, Shanghai, China. Electronic address: xiaomingfan57@sina.com.
authors: Xiaoming
authors: X
authors: Fan
mesh_terms: D002460:Cell Line; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects / Q000235:genetics*; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D053773:Transforming Growth Factor beta1; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: EMT; PTEN/Akt; miR-21