期刊
FEBS JOURNAL
卷 282, 期 24, 页码 4810-4821出版社
WILEY
DOI: 10.1111/febs.13544
关键词
hepatic stellate cells; liver fibrosis; long intergenic non-coding RNA-p21; long non-coding RNA; p21
资金
- National Natural Science Foundation of China [81000176/H0317, 81100292/H0317, 81500458/H0317]
- Zhejiang Provincial Natural Science Foundation of China [Y2090326, Y2110634, LY16H030012]
- Wenzhou Municipal Science and Technology Bureau [Y20110033, Y20120127]
- Wang Bao-En Liver Fibrosis Foundation [20100002, 20120127]
- key discipline construction project of colleges and universities in Zhejiang Province
Long non-coding RNAs are involved in various biological processes and diseases. The biological role of long intergenic non-coding RNA-p21 (lincRNA-p21) in liver fibrosis remains unknown before this study. In this study, we observed marked reduction of lincRNA-p21 expression in mice liver fibrosis models and human cirrhotic liver. Over-expression of lincRNA-p21 suppressed activation of hepatic stellate cells (HSCs) in vitro. Lentivirus-mediated lincRNA-p21 transfer into mice decreased the severity of liver fibrosis in vivo. Additionally, lincRNA-p21 reversed the activation of HSCs to their quiescent phenotype. The mRNA levels of lincRNA-p21 and p21 were positively correlated. Our results show that over-expression of lincRNA-p21 promotes up-regulation of p21 at both the mRNA and protein levels. Furthermore, lincRNA-p21 inhibited cell-cycle progression and proliferation of primary HSCs through enhancement of p21 expression. Compared with healthy subjects, serum lincRNA-p21 levels were significantly lower in patients with liver cirrhosis, especially those with decompensation. These findings collectively indicate that lincRNA-p21 is a mediator of HSC activation, supporting its utility as a novel therapeutic target for liver fibrosis.
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