Changes in microRNAs associated with hepatic stellate cell activation status identify signaling pathways

被引：105

作者：

Guo, Can-Jie ^{[1
,2
]}

Pan, Qin ^{[1
,2
]}

Cheng, Tao ^{[3
]}

Jiang, Bo ^{[4
]}

Chen, Guang-Yu ^{[1
,2
]}

Li, Ding-Guo ^{[1
,2
]}

机构：

[1] Shanghai Jiao Tong Univ, Dept Gastroenterol, Sch Med, Xinhua Hosp, Shanghai 200092, Peoples R China

[2] Shanghai Jiao Tong Univ, Digest Dis Lab, Sch Med, Xinhua Hosp, Shanghai 200092, Peoples R China

[3] Shanghai Jiao Tong Univ, Sch Med, Affiliated Peoples Hosp 6, Dept Orthopaed, Shanghai 200092, Peoples R China

[4] Cent S Univ, Sch Business, Changsha, Peoples R China

来源：

FEBS JOURNAL | 2009年 / 276卷 / 18期

关键词：

bioinformatics; hepatic stellate cells; liver fibrosis; microarray; pathway; LIVER FIBROSIS; GENE-EXPRESSION; TGF-BETA; APOPTOSIS; P38;

D O I：

10.1111/j.1742-4658.2009.07213.x

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：

Activation of hepatic stellate cells (HSCs), which is regulated by multiple signal transduction pathways, is the key event in liver fibrosis. Moreover, members of these pathways are important targets for microRNAs (miRNAs). To better understand the critical pathways of HSC activation, we performed comprehensive comparative bioinformatics analysis of microarrays of quiescent and activated HSCs. Changes in miRNAs associated with HSC activation status revealed that 13 pathways were upregulated and 22 pathways were downregulated by miRNA. Furthermore, mitochondrial integrity, based on highly upregulated Bcl-2 and downregulated caspase-9, was confirmed in HSCs and fibrotic livers by immnofluorescence assay, quantitative RT-PCR, and western blot analysis. These findings provide in vitro and in vivo evidence that the mitochondrial pathway of apoptosis plays a significant role in the progression of liver fibrogenesis via HSC activation.

引用

页码：5163 / 5176

页数：14

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