title: [Effect of TGF-b1 siRNA-mediated silencing on Smad proteins in hepatic fibrosis rats].
abstract: OBJECTIVE
  To investigate the changes in Smad 2, 3, 4 and 7 of the transforming growth factor-beta 1 (TGF-b1)/Smad signaling pathways in carbon tetrachloride (CCL4)-induced hepatic fibrosis rats treated with TGF-b1 small interfering (si)RNA.
  
  
  METHODS
  Rats were randomly divided among five groups: non-fibrotic (normal); fibrosis-induced (model); fibrotic treated with 0.125 mg/kg TGF-b1 siRNA; fibrotic treated with 0.250 mg/kg TGF-b1 siRNA; and fibrotic treated with negative control TGF-b1 siRNA. The expression of Smad 2, 3, 4 and 7 was detected by real-time polymerase chain reaction (for mRNA), immunohistochemistry and Western blotting (for protein).
  
  
  RESULTS
  The mRNA and protein levels of Smad 2, 3 and 4 were significantly lower in the the fibrotic rats treated with either 0.250 mg/kg or 0.125 mg/kg TGF-b1 siRNA than in the fibrotic model or the negative control TGF-b1 siRNA rats (P less than 0.01). Moreover, the mRNA and protein expression levels of Smad 2, 3 and 4 were significantly lower in the 0.250 mg/kg TGF-b1 siRNA group than in the 0.125 mg/kg group (P less than 0.05). Comparing the 0.250 mg/kg and 0.125 mg/kg TGF-b1 siRNA groups to the model group and the TGF-b1 siRNA negative control group showed significantly increased levels of mRNA and protein expression of Smad 7 (P less than 0.01). In addition, the expression levels of Smad 7 were significantly higher in the 0.250 mg/kg TGF-b1 siRNA group than in the 0.125 mg/kg group (P less than 0.05).
  
  
  CONCLUSIONS
  siRNA-mediated silencing of TGF-b1 in rats led to significantly reduced expression of Smad 2, 3 and 4, but significantly increased expression of Smad 7. TGF-b1 regulation of Smad signaling molecules may contribute to hepatic fibrosis in rats and represent a target of future therapeutic intervention.
authors.affiliation: Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education and Department of Infectious Diseases, the Second Affiliated Hospital, Chongqing Medical University, China.
authors.forename: Yin-chun
authors.initials: YC
authors.lastname: Sun
authors.forename: Qing
authors.initials: Q
authors.lastname: Liang
authors.forename: Ke-li
authors.initials: KL
authors.lastname: Qian
authors.forename: Lang
authors.initials: L
authors.lastname: Xiao
authors.forename: Qi
authors.initials: Q
authors.lastname: Liu
authors.forename: Xiao-feng
authors.initials: XF
authors.lastname: Shi
mesh_terms: D000818:Animals; D020868:Gene Silencing; D008103:Liver Cirrhosis / Q000378:metabolism*; D034741:RNA, Small Interfering; D051381:Rats; D051785:Smad Proteins / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000235:genetics*
chemical_list: D034741:RNA, Small Interfering; D051785:Smad Proteins; D053773:Transforming Growth Factor beta1