lincRNA-p21 inhibits hepatic stellate cell activation and liver fibrogenesis via p21

被引：57
作者：
Zheng, Jianjian [1 ]
Dong, Peihong [2 ]
Mao, Yuqing [3 ]
Chen, Shaolong [4 ]
Wu, Xiaoli [5 ]
Li, Guojun [6 ]
Lu, Zhongqiu [7 ]
Yu, Fujun [2 ]
机构：
[1] Wenzhou Med Univ, Affiliated Hosp 1, Wenzhou Key Lab Surg, Wenzhou 325000, Zhejiang, Peoples R China
[2] Wenzhou Med Univ, Affiliated Hosp 1, Dept Infect Dis, Wenzhou 325000, Zhejiang, Peoples R China
[3] Fudan Univ, Jinshan Hosp, Dept Gastroenterol, Shanghai 200433, Peoples R China
[4] Fudan Univ, Huashan Hosp, Dept Infect Dis, Shanghai 200433, Peoples R China
[5] Wenzhou Med Univ, Affiliated Hosp 1, Dept Gastroenterol, Wenzhou, Peoples R China
[6] Ningbo Yinzhou Second Hosp, Dept Hepatol, Ningbo, Peoples R China
[7] Wenzhou Med Univ, Affiliated Hosp 1, Dept Emergency, Wenzhou 325000, Zhejiang, Peoples R China
来源：
FEBS JOURNAL | 2015年 / 282卷 / 24期
基金：
中国国家自然科学基金;
关键词：
hepatic stellate cells; liver fibrosis; long intergenic non-coding RNA-p21; long non-coding RNA; p21; LONG NONCODING RNA; COLORECTAL-CANCER; FEEDBACK LOOP; PROLIFERATION; CARCINOMA; FIBROSIS; EXPRESSION; APOPTOSIS; BIOMARKER; RNA-P21;
D O I：
10.1111/febs.13544
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
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.
引用
收藏
页码：4810 / 4821
页数：12
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