Regulation of hypoxia-inducible factor-1α by cyclical mechanical stretch in rat vascular smooth muscle cells
Regulation of hypoxia-inducible factor-1α by cyclical mechanical stretch in rat vascular smooth muscle cells
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DOI：
10.1042/cs20030088
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发表时间：
2003-10-01
期刊：
影响因子：
6
通讯作者：
Kuan, PL
中科院分区：
文献类型：
--
作者：
Chang, H;Shyu, KG;Kuan, PL
血管平滑肌细胞（VSMCs）在体内暴露于激素和机械应力下。激素因素已被证明影响缺氧诱导因子-1 α (hif -1 α)。机械应力如何影响VSMCs中hif -1 α的调节此前尚未报道，因此我们试图研究培养大鼠VSMCs中周期性机械拉伸对hif -1 α的调节。在柔性膜基底上生长的大鼠VSMCs以60 cycles/min的速度真空拉伸至最大伸长率的20%。HIF-1alpha蛋白质的水平开始提高早在2 h后应用,达到了2.8倍的最大控制4 h。实时PCR表明HIF-1alpha mRNA水平增加2.1倍周期性拉伸后4 h。周期性机械拉伸也增加了免疫组织化学标签HIF-1alpha VSMCs周期性拉伸后4 h。第42页的磷酸化/ p44增殖蛋白激酶(MAP激酶)增加拉伸后被MAP激酶抑制剂PD98059和U0126抑制。PD98059和U0126也能抑制周期性拉伸诱导的HIF-1alpha基因表达。综上所述，周期性机械拉伸激活了培养VSMCs中hif -1 α的基因表达，这种机械作用可能是通过p42/p44 MAP激酶途径介导的。
Vascular smooth muscle cells (VSMCs) are exposed to hormonal and mechanical stress in vivo. Hormonal factors have been shown to affect hypoxia-inducible factor-1alpha (HIF-1alpha). How mechanical stress affects the regulation of HIF-1alpha in VSMCs has not been reported previously, and therefore we sought to investigate the regulation of HIF-1alpha by cyclical mechanical stretch in cultured rat VSMCs. Rat VSMCs grown on a flexible membrane base were stretched by vacuum to 20% of the maximum elongation at 60 cycles/min. The levels of HIF-1alpha protein began to increase as early as 2 h after stretch was applied and reached a maximum of 2.8-fold over the control by 4 h. Real-time PCR showed that the levels of HIF-1alpha mRNA increased 2.1-fold after cyclical stretch for 4 h. Cyclical mechanical stretch also increased the immunohistochemical labelling of HIF-1alpha in VSMCs after cyclical stretch for 4 h. The phosphorylation of p42/p44 mitogen-activated protein kinase (MAP kinase) increased after stretch and this was inhibited by the MAP kinase kinase inhibitors PD98059 and U0126. PD98059 and U0126 also blocked HIF-1alpha gene expression induced by cyclical stretch. In conclusion, cyclical mechanical stretch activates the gene expression of HIF-1alpha in cultured VSMCs and this mechanical effect is possibly mediated by the p42/p44 MAP kinase kinase pathway.