title: Down-regulation of tTG expression by RNAi inhibits HSC proliferation and attenuates liver fibrosis.
abstract: OBJECTIVE
  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.
authors: Department of General Surgery, Renji Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai, 200127, China.
authors: Gang
authors: G
authors: Zhao
authors: Zhi-Qi
authors: ZQ
authors: Zhang
authors: Bin
authors: B
authors: Zhang
authors: Meng
authors: M
authors: Luo
authors: Yong-Wei
authors: YW
authors: Sun
authors: Zhi-Yong
authors: ZY
authors: Wu
mesh_terms: D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D002478:Cells, Cultured; D018450:Disease Progression; D015536:Down-Regulation; D005822:Genetic Vectors; D055166:Hepatic Stellate Cells / Q000166:cytology / Q000201:enzymology / Q000502:physiology*; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D008103:Liver Cirrhosis / Q000235:genetics / Q000517:prevention & control*; D008297:Male; D034741:RNA, Small Interfering / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011503:Transglutaminases / Q000235:genetics* / Q000378:metabolism
chemical_list: D034741:RNA, Small Interfering; D011503:Transglutaminases