Yang Meimei, Fang Jing, Liu Qingan, Wang Yan, Zhang Zhuobo
The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150081, PR China.
The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150081, PR China.
Biochem Biophys Res Commun. 2017 Dec 16;494(3-4):526-533. doi: 10.1016/j.bbrc.2017.10.122. Epub 2017 Oct 25.
This study investigated the change of transient receptor potential cation channel subfamily M member 7 (TRPM7) expression in rat aortic vascular smooth muscle cells (RAoSMCs) treated with a high concentration of d-glucose (HG) and its role in promoting the proliferative phenotype of RAoSMCs. Chronic exposure to HG increased TRPM7 protein expression and TRPM7 whole-cell currents in RAoSMCs. By contrast, RAoSMC exposure to high concentration of l-glucose and mannital exhibited no such effect. Mechanistically, HG treatment elevated TRPM7 expression by increasing oxidative stress. Data also demonstrated that HG significantly promoted RAoSMC proliferation. In addition, as indicated by the changes of the expression of VSMC differentiation marker molecules, phenotype switching of RAoSMCs occurred during exposing to HG. TRPM7 knockdown partially blocked the HG effect on phenotype switching and RAoSMC proliferation. This phenomenon was achieved through inhibiting the mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (MEK)-ERK signaling pathway. These observations suggest that reactive oxygen species-TRPM7-ERK1/2 axis plays an important role in hyperglycemia-induced development of the proliferative phenotype in RAoSMC.
本研究调查了高浓度d-葡萄糖（HG）处理的大鼠主动脉血管平滑肌细胞（RAoSMCs）中瞬时受体电位阳离子通道亚家族M成员7（TRPM7）表达的变化及其在促进RAoSMCs增殖表型中的作用。长期暴露于HG会增加RAoSMCs中TRPM7蛋白表达和TRPM7全细胞电流。相比之下，RAoSMCs暴露于高浓度的l-葡萄糖和甘露醇则无此效应。机制上，HG处理通过增加氧化应激来提高TRPM7表达。数据还表明，HG显著促进RAoSMC增殖。此外，正如血管平滑肌细胞（VSMC）分化标志物分子表达的变化所示，RAoSMCs在暴露于HG期间发生了表型转换。TRPM7基因敲低部分阻断了HG对表型转换和RAoSMC增殖的作用。这种现象是通过抑制丝裂原活化蛋白激酶/细胞外信号调节激酶（ERK）激酶（MEK）-ERK信号通路实现的。这些观察结果表明，活性氧-TRPM7-ERK1/2轴在高血糖诱导的RAoSMC增殖表型发展中起重要作用。
