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- 2018
Smad7修饰的骨髓间充质干细胞通过肝星状细胞Smads信号与MMP-1/TIMP-1平衡的抗肝纤维化机制
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Abstract:
摘要 目的:探究Smad7修饰的骨髓间充质干细胞(Smad7-BMSCs)在体外抑制肝纤维化的潜在机制.方法:实验将大鼠肝星状细胞HSC-T6分为A组、B组,分别与Smad7-BMSCs和PBS共同培养.通过ELISA法检测各组细胞培养液中Col1和HA的含量;MTT法检测各组细胞增殖情况;培养72 h,收集细胞并提取总RNA和总蛋白,采用RT-PCR法检测细胞中Smad7、Smad3、MMP-1、TIMP-1、Col1 mRNA的表达;Western blot检测细胞中Smad7、Smad3、p-Smad3、MMP-1、TIMP-1、Col1蛋白的表达.结果:①A组细胞培养液中Col1和HA的含量显著下降(P<0.05);②A组细胞增殖显著降低(P<0.01);③Western和PCR 结果显示,A组细胞中Smad7、MMP-1的蛋白和mRNA 表达水平较B组显著升高(P<0.01),而p-Smad3、TIMP-1及Col1蛋白和mRNA 表达水平显著降低(P<0.01).结论:Smad7修饰的骨髓间充质干细胞BMSCs可能通过降低肝星状细胞Smad3蛋白的磷酸化,从而影响MMP-1/TIMP-1平衡,促进星状细胞外基质ECM的降解而实现抗肝纤维化的作用.
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