Role of ROS-TRPM7-ERK1/2 axis in high concentration glucose-mediated proliferation and phenotype switching of rat aortic vascular smooth muscle cells
Abstract 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. Highlights High concentration of D-glucose (HG) induces phenotype switching of rat aortic vascular smooth muscle cells (RAoSMCs). HG upregulates the expression of transientreceptor potential cation channel subfamily M member 7 (TRPM7) in RAoSMCs. HG-induced oxidative stress is responsible for the upregulation of TRPM7 in RAoSMCs. TRPM7-mediated activation of MEK/ERK pathway is responsible for HG-induced phenotype switching of RAoSMCs.
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