microRNA-29b prevents liver fibrosis by attenuating hepatic stellate cell activation and inducing apoptosis through targeting PI3K/AKT pathway
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摘要microRNA-29b (miR-29b) is known to be associated with TGF-beta-mediated fibrosis, but the mechanistic action of miR-29b in liver fibrosis remains unclear and is warranted for investigation. We found that miR-29b was significantly downregulated in human and mice fibrotic liver tissues and in primary activated HSCs. miR-29b downregulation was directly mediated by Smad3 through binding to the promoter of miR-29b in hepatic stellate cell (HSC) line LX1, whilst miR-29b could in turn suppress Smad3 expression. miR-29b transduction in the liver of mice prevented CCl4 inducedfibrogenesis, concomitant with decreased expression of a-SMA, collagen I and TIMP-1. Ectopic expression of miR-29b in activated HSCs (LX-1, HSC-T6) inhibited cell viability and colony formation, and caused cell cycle arrest in G1 phase by downregulating cyclin D1 and p21cip1. Further, miR-29b induced apoptosis in HSCs mediated by caspase-9 and PARP. miR-29b inhibited its downstream effectors of PIK3R1 and AKT3 through direct targeting their 3' UTR regions. Moreover, knockdown of PIK3R1 or AKT3 suppressed a-SMA and collagen I and induced apoptosis in both HSCs and in mice. In conclusion, miR-29b prevents liver fibrogenesis by inhibiting HSC activation and inducing HSC apoptosis through inhibiting PI3K/AKT pathway. These results provide novel mechanistic insights for the anti-fibrotic effect of miR-29b.
著者Wang J, Chu ESH, Chen HY, Man K, Go MYY, Huang XR, Lan HY, Sung JJY, Yu J
期刊名稱Oncotarget
出版年份2015
月份3
日期30
卷號6
期次9
出版社IMPACT JOURNALS LLC
頁次7325 - 7338
國際標準期刊號1949-2553
語言英式英語
關鍵詞AKT3; hepatic stellate cell; liver fibrosis; miR-29b
Web of Science 學科類別Cell Biology; Oncology

上次更新時間 2020-10-10 於 23:33