临床肝胆病杂志2013，Vol.29Issue(4)：290-293,4.
法尼酯衍生物X受体活化对肝星状细胞TIMP-1、TIMP-2及MMP-2表达的调节作用
Regulatory effeots of FXR activation on expression of TIMP-1, TIMP-2 and MMP-2 in hepatic stellate cells
陈科全 1周碧瑶 1陈雅莹 1邹原方 2周宇3
作者信息
- 1. 广州医学院第一附属医院消化内科,广州510120
- 2. 中山大学附属东华医院肾内风湿科,广东东莞523000
- 3. 广东医学院附属医院消化内科,广东湛江524000
- 折叠
摘要
Abstract
Objective To determine whether the regulator of bile acid and carbohydrate metabolism in hepatic stellate cells ( HSCs) , Far-nesoid X receptor ( FXR) , mediates the expression of fibrosis - related genes tissue inhibitor of matrix metalloproteinase ( TIMP) - 1 , TIMP
- 2, and matrix metalloproteinase - 2 ( MMP - 2). Methods An in vitro cell culture system with the rat HSC - T6 line was used to evaluate the effects of FXR by treating with the synthetic FXR agonist GW4064 at various concentrations (0. 01 , 0. 1 and 1 μmol/L) for 18 h. Untreated cells served as controls. The mRNA levels of FXR, TIMP - 1 , TIMP - 2, and MMP - 2 were measured by real - time reverse transcription PCR. The protein levels of TIMP - 1 , TIMP - 2, and MMP - 2 were determined by western blotting. The significance of intergroup differences was assessed by single - factor one - way ANOVA statistical analysis. Results Treatment with GW4064 led to significantly increased mRNA expression of FXR (0.01 μmol/L vs. control, P <0. 01 ). While the 0. 1 μmol/L concentration of GW4064 stimulated a significantly higher level of FXR mRNA expression than the 0. 01 μmol/L concentration (P <0. 01) , the level was not significantly different from that stimulated by the 1 μmol/L concentration ( P > 0. 05 ) . Unlike the 0.01 μmol/L concentration of GW4064, the 0. 1 and 1 μmol/L concentrations reduced the TIMP - 1 and TIMP - 2 mRNA and protein expressions to levels significantly lower than that in the controls ( all P
< 0. 05). GW4064 treatment increased MMP - 2 mRNA and protein expressions and the 1 μmol/L mediated increase was significantly higher than that of the control (P <0. 01). Conclusion Activation of FXR on HSCs may contribute to fibrosis by down - regulating TIMP - 1 and TIMP - 2 and up - regulating MMP - 2 , which mediate the balance of extracellular matrix synthesis and degradation; thus, FXR ligands may represent useful therapeutic targets of liver fibrosis.关键词
星形细胞/肝细胞/肝硬化/基质金属蛋白酶类Key words
astrocytes/hepatocytes/liver cirrhosis/matrix metalloproteinases分类
医药卫生引用本文复制引用
陈科全,周碧瑶,陈雅莹,邹原方,周宇..法尼酯衍生物X受体活化对肝星状细胞TIMP-1、TIMP-2及MMP-2表达的调节作用[J].临床肝胆病杂志,2013,29(4):290-293,4.
