流体剪切应力对大鼠骨髓间充质干细胞MT1-MMP基因表达的影响
唐 杰, 孙晓东, 袁雅红, 李瑞明, 彭兴春, 王汉琴
中国临床解剖学杂志 ›› 2010, Vol. 28 ›› Issue (6) : 680.
流体剪切应力对大鼠骨髓间充质干细胞MT1-MMP基因表达的影响
Effects of laminar shear stress on expression of MT1-MMP in rat bone marrow-derived mesenchymal stem cells
目的 探讨流体剪切应力对大鼠骨髓间充质干细胞(rat bone marrow-derived mesenchymal stem cells,rMSCs)中膜型基质金属蛋白酶1(Membrane type-1 matrix metalloproteinase, MT1-MMP)基因表达的影响,为阐明应力诱导rMSCs分化的分子机制提供一些实验依据。 方法 应用平行平板流动腔系统,给rMSCs施加不同大小和不同加载时间的层流剪切应力,用real-time PCR检测MT1-MMP基因mRNA的表达水平。 结果 5, 15, 30 dynes/cm2剪切应力均能刺激rMSCs的MT1-MMP mRNA表达,且其作用呈时间依赖和强度依赖。p38抑制剂(SB202190)可以明显抑制这种作用, 而PI3K抑制剂(wortmannin)却增强了这种效果。 结论 流体剪切应力可诱导rMSCs的MT1-MMP基因表达,其表达量与刺激时间和剪切应力的强度密切相关,这种作用可能通过p38MAPK和PI3K/Akt信号通路。
Objective To investigate the effect of laminar shear stress on the expression of membrane type-1 matrix metalloproteinase(MT1-MMP)in rat bone marrow-derived mesenchymal stem cells (rMSCs). Methods rMSCs were isolated from SD rat lower extremities and loaded by laminar shear stress with the parallel-plate flow chamber system, then the expression of MT1-MMP mRNA of rMSCs was examined by real-time PCR. Results Shear stress with different magnitude of 5, 15, 30 dynes/cm2 all induced MT1-MMP mRNA expression, especially high shear stress, 30 dynes/cm2, which was time-dependent. The expression of MT1-MMP mRNA was inhibited by SB202190, an inhibitor of p38, but enhanced by wortmannin, an inhibitor of PI3K/Akt. Conclusion Shear stress can activate the expression of MT1-MMP. The amount of MT1-MMP expression is closely related to stimulating time and the strengths of shear stress, and p38MAPK and PI3K/Akt signal pathway may play a critical role during the process.
间充质干细胞 / 膜型基质金属蛋白酶1 / 剪切应力
Mesenchymal stem cells / Mmembrane type-1 matrix metalloproteinase / Laminar shear stress
国家自然科学基金(30770535);湖北省高等学校优秀中青年科技创新团队计划(T201008);湖北医药学院博士启动金(2007QDJ7)
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