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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 (miR-NAs). To better understand the critical pathways of HSC activation, we performed comprehensive comparative bioinformatics analysis of micro-arrays of quiescent and activated HSCs. | Changes in microRNAs associated with hepatic stellate cell activation status identify signaling pathways Can-Jie Guo1 z Qin Pan1 z Tao Cheng2 Bo Jiang3 Guang-Yu Chen1 and Ding-Guo Li1 1 Digestive Disease Laboratory and Department of Gastroenterology Xinhua Hospital Schoolof Medicine Shanghai Jiaotong University China 2 Department of Orthopaedics The Sixth Affiliated People s Hospital Schoolof Medicine Shanghai Jiaotong University China 3 Business School CentralSouth University Changsha China Keywords bioinformatics hepatic stellate cells liver fibrosis microarray pathway Correspondence D. G. Li Department of Gastroenterology Xinhua Hospital No. 1665 Kongjiang Road Shanghai 200092 China Fax 86 21 62712237 Tel 86 21 62712237 E-mail lidingguo13612@yahoo.com.cn Q. Pan Department of Gastroenterology Xinhua Hospital No. 1665 Kongjiang Road Shanghai 200092 China Fax 86 21 62712237 Tel 86 21 62712237 E-mail pan_qin@yeah.net These authors contributed equally to this work Received 9 April2009 revised 9 July 2009 accepted 14 July 2009 doi 10.1111 j.1742-4658.2009.07213.x 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 miR-NAs . 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 .
