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Effect of ursodeoxycholic acid on TGF beta1/Smad signaling pathway in rat hepatic stellate cells

LIANG Tie-jun YUAN Jun-hua TAN Yan-rong REN Wan-hua HAN Guo-qing ZHANG Jie WANG Lai-cheng QIN Cheng-yong

中华医学杂志(英文版)2009,Vol.122Issue(10):1209-1213,5.
中华医学杂志(英文版)2009,Vol.122Issue(10):1209-1213,5.DOI:10.3760/cma.j.issn.0366-6999.2009.10.018

Effect of ursodeoxycholic acid on TGF beta1/Smad signaling pathway in rat hepatic stellate cells

Effect of ursodeoxycholic acid on TGF beta1/Smad signaling pathway in rat hepatic stellate cells

LIANG Tie-jun 1YUAN Jun-hua 1TAN Yan-rong 1REN Wan-hua 1HAN Guo-qing 1ZHANG Jie 2WANG Lai-cheng 2QIN Cheng-yong1

作者信息

  • 1. Department of Digestive Diseases Provincial Hospital Affiliated to Shandong University,Jinan, Shandong 250021, China
  • 2. Central Laboratory Provincial Hospital Affiliated to Shandong University,Jinan, Shandong 250021, China
  • 折叠

摘要

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 (TGFβ1)/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 TGFβ1, TGF type I receptor, Smad3, Smad4 and Smad7 were measured by Western blotting, as well as the expressions of TGFβ1, 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 TGFβ1 in the high and middle UDCA dose groups for 24 hours and 48 hours significantly decreased (P <0.05), the protein expressions of TGFβ1 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 close 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 close 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).Conclusion UDCA could curb the development of hepatic fibrosis through affecting the signaling pathway of TGFβ1/Smad by inhibiting the expressions of TGFβ1, Smad3 and CBP and increasing the expression of Smad7.

关键词

ursodeoxycholic acid, hepatic stellate cells/transforming growth factor-betal/Smad signaling pathway

Key words

ursodeoxycholic acid, hepatic stellate cells/transforming growth factor-betal/Smad signaling pathway

分类

医药卫生

引用本文复制引用

LIANG Tie-jun,YUAN Jun-hua,TAN Yan-rong,REN Wan-hua,HAN Guo-qing,ZHANG Jie,WANG Lai-cheng,QIN Cheng-yong..Effect of ursodeoxycholic acid on TGF beta1/Smad signaling pathway in rat hepatic stellate cells[J].中华医学杂志(英文版),2009,122(10):1209-1213,5.

基金项目

This study was supported by a grant from Shandong Province Technology Development Project (No. 2005GG3202192). (No. 2005GG3202192)

中华医学杂志(英文版)

OACSTPCDMEDLINESCI

0366-6999

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