TGF-β-induced hepatocyte lincRNA-p21 contributes to liver fibrosis in mice

被引：36

作者：

Tu, Xiaolong ^{[1
]}

Zhang, Yuanyuan ^{[1
]}

Zheng, Xiuxiu ^{[1
]}

Deng, Jia ^{[1
]}

Li, Huanan ^{[1
]}

Kang, Zhiqian ^{[1
]}

Cao, Zhipeng ^{[1
]}

Huang, Zhen ^{[1
]}

Ding, Zhi ^{[1
]}

Dong, Lei ^{[1
]}

Chen, Jiangning ^{[1
]}

Zang, Yuhui ^{[1
]}

Zhang, Junfeng ^{[1
,2
]}

机构：

[1] Nanjing Univ, Sch Life Sci, State Key Lab Pharmaceut Biotechnol, Nanjing 210093, Jiangsu, Peoples R China

[2] Jiangsu Engn Res Ctr microRNA Biol & Biotechnol, Nanjing 210093, Jiangsu, Peoples R China

来源：

SCIENTIFIC REPORTS | 2017年 / 7卷

基金：

中国国家自然科学基金;

关键词：

LONG-NONCODING-RNA; HEPATIC STELLATE CELLS; HEPATOCELLULAR-CARCINOMA; UP-REGULATION; APOPTOSIS; EXPRESSION; GENE; PROLIFERATION; PROMOTES; DISRUPTION;

D O I：

10.1038/s41598-017-03175-0

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Hepatocyte death, as well as the following inflammatory and fibrogenic signaling cascades, is the key trigger of liver fibrosis. Here, we isolated hepatocytes from CCl4-induced fibrotic liver and found that hepatocyte lincRNA-p21 significantly increased during liver fibrosis. The increase of hepatocyte lincRNA-p21 was associated with the loss of miR-30, which can inhibit TGF-beta signaling by targeting KLF11. We revealed that lincRNA-p21 modulated miR-30 availability by acting as a competing endogenous RNA (ceRNA). The physiological significance of this interaction is highlighted by the feedback loop, in which lincRNA-p21 works as a downstream effector of the TGF-beta signaling to strengthen TGF-beta signaling and mediate its role in promoting liver fibrosis by interacting with miR-30. In vivo results showed that knockdown of hepatocyte lincRNA-p21 greatly reduced CCl4-induced liver fibrosis and inflammation, whereas ectopic expression of miR-30 in hepatocyte exhibited the similar results. Mechanistic studies further revealed that inhibition of miR-30 impaired the effects of lincRNA-p21 on liver fibrosis. Additionally, lincRNA-p21 promoted hepatocyte apoptosis in vitro and in vivo, whereas the proliferation rate of hepatocyte was suppressed by lincRNA-p21. The pleiotropic roles of hepatocyte lincRNA-p21 suggest that it may represent an unknown paradigm in liver fibrosis and serve as a potential target for therapy.

引用

页数：14

共 45 条

[1] Liver fibrosis [J].