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Inhibition of connective tissue growth factor suppresses hepatic stellate cell activation in vitro and prevents liver fibrosis in vivo

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Abstract

Activation of hepatic stellate cells (HSC) represents a critical event in fibrosis, and connective tissue growth factor (CTGF) plays a profibrotic activity and a key factor in the pathogenesis of tissue fibrosis. The current study aimed to determine whether lentivirus-mediated short hairpin RNA (shRNA)–targeted CTGF downregulates the CTGF expression and furthermore whether it suppresses the activation and proliferation of HSC in vitro and prevents liver fibrosis in vivo. HSC-T6 cells were treated with recombinant lentivirus carrying CTGF siRNA. Real-time PCR, Western blotting, MTT, and flow cytometry were performed to investigate the activation and proliferation of HSC-T6 cells in response to CTGF silence. CCl4-induced rats were received lentivirus containing CTGF siRNA by intraportal vein injection. Levels of liver fibrosis were assessed by biochemical and histopathologic examinations. Recombinant lentivirus containing CTGF siRNA could effectively and specifically downregulate the expression of CTGF in both HSC-T6 cells and CCl4-induced rats with liver fibrosis. Blockade of CTGF resulted in significant inhibition of HSC activation and proliferation with decrease in TIMPs, MMP2, MMP9, and collagen I, as well as increase in cells in S phase. Silencing CTGF expression with siRNA prevented liver fibrosis in CCl4-induced rat model. These findings indicated that CTGF plays a key role in the pathogenesis of liver fibrosis and lentiviral-mediated CTGF siRNA has the potential to be an effective treatment for liver fibrosis.

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Acknowledgments

This work was supported by the grant from National Natural Science Foundation of China (No. 30571658).

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Authors and Affiliations

  1. Department of Infectious Diseases, Tangdu Hospital, Fourth Military Medical University, 1 Xinsi Road, Xi’an, 710038, Shannxi Province, China

    Chunqiu Hao, Yumei Xie, Meijuan Peng, Li Ma, Yun Zhou, Yan Zhang, Wenzhen Kang, Jiuping Wang, Xuefan Bai, Pingzhong Wang & Zhansheng Jia

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  1. Chunqiu Hao
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  2. Yumei Xie
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  3. Meijuan Peng
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  4. Li Ma
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Correspondence to Pingzhong Wang or Zhansheng Jia.

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Hao, C., Xie, Y., Peng, M. et al. Inhibition of connective tissue growth factor suppresses hepatic stellate cell activation in vitro and prevents liver fibrosis in vivo. Clin Exp Med 14, 141–150 (2014). https://doi.org/10.1007/s10238-013-0229-6

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  • DOI: https://doi.org/10.1007/s10238-013-0229-6

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