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Changes in microRNAs associated with hepatic stellate cell activation status identify signaling pathways
Author(s) -
Guo CanJie,
Pan Qin,
Cheng Tao,
Jiang Bo,
Chen GuangYu,
Li DingGuo
Publication year - 2009
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2009.07213.x
Subject(s) - hepatic stellate cell , microrna , signal transduction , microbiology and biotechnology , biology , cell , computational biology , genetics , gene , endocrinology
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.