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

ABSTRACT: 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 CCl(4) in rat livers at week 8 and week 12 after injection of CCl(4). 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.

SUBMITTER: Zhao G

PROVIDER: S-EPMC3127072 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature

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

Zhao Gang G Zhang Zhi-Qi ZQ Zhang Bin B Luo Meng M Sun Yong-Wei YW Wu Zhi-Yong ZY

International journal of clinical and experimental pathology 20110612 5

<h4>Purpose</h4>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.<h4>Methods</h4>In this study, primary hepatic stellate cells were isolated, purified, and cultured from rat. Expression of tTG gene was downregulated by lentiviru ...[more]

PMID: 21738822

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

Publications

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

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