Down-regulation of tTG expression by RNAi inhibits HSC proliferation and attenuates liver fibrosis

International Journal of Clinical and Experimental Pathology

Gang Zhao¹  Zhi-Qi Zhang¹  Meng Luo¹  Zhi-Yong Wu¹  Bin Zhang¹  Yong-Wei Sun¹ 

关键词: Tissue transglutaminase;    RNAi;    hepatic stellate cells;    liver fibrosis;    lentiviral vector;   

DOI  :  

学科分类：生理学与病理学

来源: e-Century Publishing Corporation

【 摘 要 】

Purpose: Expressed in hepatic stellate cell (HSC), tTG is involved in fibrotic diseases including human hepatic fibrosis by promoting the cross-linking of ECM and participating in the initiation and/or progression of liver fibrosis. The purpose of this study is to identify whether depletion of tTG could attenuate liver fibrosis. Methods: In this study, primary hepatic stellate cells were isolated, purified, and cultured from rat. Expression of tTG gene was downregulated by lentivirus-mediated RNAi, and the effects on the activation, proliferation and apoptosis of HSC were investigated both in vitro and in vivo. Results: Lentivirus-mediated RNAi successfully reduced the endogenous expression of tTG in cultured cells. The down-regulation of tTG markedly inhibited the proliferation of HSC and attenuated the synthesis of Collagen-1. The downregulation of tTG also markedly reduced the level of tTG and hydroxyproline induced by CCl₄ in rat livers at week 8 and week 12 after injection of CCl₄. Conclusions: In summary, tTG plays an important role in liver fibrosis. Lentivirus-mediated downregulation of tTG showed a potential anti-fibrosis effect in rats, providing new evidence that the involvement of tTG in HSC activation, also suggesting that RNAi-directed targeting of tTG may be used as a potent and specific therapeutic tool for the treatment of liver fibrosis, especially in inhibiting the activation of HSC.

【 授权许可】

Unknown