Journal
FEBS JOURNAL
Volume 276, Issue 18, Pages 5163-5176Publisher
WILEY
DOI: 10.1111/j.1742-4658.2009.07213.x
Keywords
bioinformatics; hepatic stellate cells; liver fibrosis; microarray; pathway
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Funding
- Foundation of Shanghai Commission of Science Technology of Research Program [O7JC14044]
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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.
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