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

Authors

  • Can-Jie Guo,

    1.  Digestive Disease Laboratory and Department of Gastroenterology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, China
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    • These authors contributed equally to this work

  • Qin Pan,

    1.  Digestive Disease Laboratory and Department of Gastroenterology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, China
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    • These authors contributed equally to this work

  • Tao Cheng,

    1.  Department of Orthopaedics, The Sixth Affiliated People’s Hospital, School of Medicine, Shanghai Jiaotong University, China
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  • Bo Jiang,

    1.  Business School, Central South University, Changsha, China
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  • Guang-Yu Chen,

    1.  Digestive Disease Laboratory and Department of Gastroenterology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, China
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  • Ding-Guo Li

    1.  Digestive Disease Laboratory and Department of Gastroenterology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, China
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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

Abstract

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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