Liu Li, Jiang Hui-qing, Zhang Xiao-lan, Zhao Dong-qiang
Department of Gastroenterology, the Second Hospital of Hebei Medical Univesity, Shijiazhuang 050000, China.
Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2007 Nov;23(4):482-6.
To investigate the effect of IH764-3 on the expression of MMP-13 and TIMP-1 by H2O2-stimulated hepatic stellate cell and the alteration of FAK during this process.
The expression of MMP-13 and FAK mRNA was examined by RT-PCR. TIMP-1 mRNA was analyzed by in-situ hybridization. FAK and TIMP-1 were evaluated at protein level through Western blotting method.
Being incubated for 2 h, compared with control group, MMP-13 mRNA was upregulated by IH764-3, but TIMP-1 transcription was reduced in a dose-dependent manner, accompanied with the decrease of FAK mRNA. The expression of TIMP-1 and FAK protein in HSC also decreased after being exposed by IH764-3 for 24 h.
IH764-3 can induce the expression of MMP-13 and inhibit the expression of TIMP-1. Down-regulating the expression of FAK mRNA may be one of its mechanisms.
研究IH764-3对过氧化氢刺激的肝星状细胞中基质金属蛋白酶-13(MMP-13)和基质金属蛋白酶组织抑制因子-1(TIMP-1)表达的影响以及在此过程中粘着斑激酶(FAK)的变化。
采用逆转录聚合酶链反应(RT-PCR)检测MMP-13和FAK mRNA的表达。通过原位杂交分析TIMP-1 mRNA。采用蛋白质印迹法在蛋白质水平评估FAK和TIMP-1。
孵育2小时后,与对照组相比,IH764-3上调了MMP-13 mRNA,但TIMP-1转录呈剂量依赖性降低,同时伴有FAK mRNA的减少。IH764-3作用24小时后,肝星状细胞中TIMP-1和FAK蛋白的表达也降低。
IH764-3可诱导MMP-13的表达并抑制TIMP-1的表达。下调FAK mRNA的表达可能是其作用机制之一。