title: Effect of ursodeoxycholic acid on TGF beta1/Smad signaling pathway in rat hepatic stellate cells.
abstract: BACKGROUND
  Hepatic fibrosis is the key stage of the pathological progress from hepatic injury to cirrhosis. Ursodeoxycholic acid (UDCA) has been known as having significant clinical therapeutic effects on chronic liver diseases. Our research aimed to study the effect of UDCA on the signaling pathway of transforming growth factor beta1 (TGFbeta1)/Smad and discuss its possible molecular mechanisms of inhibiting hepatic fibrosis.
  
  
  METHODS
  Rat hepatic stellate cells were cultured in vitro and randomly assigned to 4 groups. Group A was control group, with only DMEM culture medium applied, and groups B, C, D were experimental groups, with different doses of UDCA (1.0 mmol/L, 0.5 mmol/L and 0.25 mmol/L respectively) added into their DMEM culture medium for further culture of 24 hours and 48 hours. The protein expressions of TGFbeta1, TGF type I receptor, Smad3, Smad4 and Smad7 were measured by Western blotting, as well as the expressions of TGFbeta1, Smad3, Smad7 and cAMP response element (CREB) binding protein (CBP) mRNA by real-time PCR. SPSS 11.5 statistical package was adopted for data analyses.
  
  
  RESULTS
  Compared with control group, the mRNA expressions of TGFbeta1 in the high and middle UDCA dose groups for 24 hours and 48 hours significantly decreased (P < 0.05), the protein expressions of TGFbeta1 in the two above groups for 48 hours and in the high dose group for 24 hours significantly decreased (P < 0.05). The protein and mRNA expressions of Smad3 in each UDCA dose group for 24 hours and 48 hours significantly decreased, with significant difference among different UDCA dose groups and between that of 24 hours and 48 hours observed (P < 0.05). The protein and mRNA expressions of Smad7 in the high and middle UDCA dose groups for 24 hours and 48 hours significantly increased. The CBP mRNA expression in each UDCA dose group for 24 hours and 48 hours significantly decreased (P < 0.05), with significant difference among different UDCA dose groups observed (P < 0.05).
  
  
  CONCLUSIONS
  UDCA could curb the development of hepatic fibrosis through affecting the signaling pathway of TGFbeta1/Smad by inhibiting the expressions of TGFbeta1, Smad3 and CBP and increasing the expression of Smad7.
authors.affiliation: Department of Digestive Diseases, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China.
authors.forename: Tie-jun
authors.initials: TJ
authors.lastname: Liang
authors.forename: Jun-hua
authors.initials: JH
authors.lastname: Yuan
authors.forename: Yan-rong
authors.initials: YR
authors.lastname: Tan
authors.forename: Wan-hua
authors.initials: WH
authors.lastname: Ren
authors.forename: Guo-qing
authors.initials: GQ
authors.lastname: Han
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.forename: Lai-cheng
authors.initials: LC
authors.lastname: Wang
authors.forename: Cheng-yong
authors.initials: CY
authors.lastname: Qin
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D002756:Cholagogues and Choleretics / Q000494:pharmacology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics; D055166:Hepatic Stellate Cells / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D016133:Polymerase Chain Reaction; D051381:Rats; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D051785:Smad Proteins / Q000378:metabolism*; D051900:Smad3 Protein / Q000235:genetics / Q000378:metabolism; D051901:Smad4 Protein / Q000378:metabolism; D051906:Smad7 Protein / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D014580:Ursodeoxycholic Acid / Q000494:pharmacology*
chemical_list: D002756:Cholagogues and Choleretics; D017362:Cyclic AMP Response Element-Binding Protein; D018125:Receptors, Transforming Growth Factor beta; D051785:Smad Proteins; D051900:Smad3 Protein; D051901:Smad4 Protein; C490811:Smad4 protein, rat; D051906:Smad7 Protein; C497808:Smad7 protein, rat; D053773:Transforming Growth Factor beta1; D014580:Ursodeoxycholic Acid