TRPM7 regulates vascular endothelial cell adhesion and tube formation

Abstract

sient receptor potential melastatin 7 (TRPM7) is a nonselective cation channel with an ␣-kinase domain in its COOH terminal, known to play a role in diverse physiological and pathological processes such as Mg 2ϩ homeostasis, cell proliferation, and hypoxic neuronal injury. Increasing evidence suggests that TRPM7 contributes to the physiology/pathology of vascular systems. For example, we recently demonstrated that silencing TRPM7 promotes growth and proliferation and protects against hyperglycemia-induced injury in human umbilical vein endothelial cells (HUVECs). Here we investigated the potential effects of TRPM7 on morphology, adhesion, migration, and tube formation of vascular endothelial cells and the potential underlying mechanism. We showed that inhibition of TRPM7 function in HUVECs by silencing TRPM7 decreases the density of TRPM7-like current and cell surface area and inhibits cell adhesion to Matrigel. Silencing TRPM7 also promotes cell migration, wound healing, and tube formation. Further studies showed that the extracellular signalregulated kinase (ERK) pathway is involved in the change of cell morphology and the increase in HUVEC migration induced by TRPM7 silencing. We also demonstrated that silencing TRPM7 enhances the phosphorylation of myosin light chain (MLC) in HUVECs, which might be involved in the enhancement of cell contractility and motility. Collectively, our data suggest that the TRPM7 channel negatively regulates the function of vascular endothelial cells. Further studies on the underlying mechanism may facilitate the development of the TRPM7 channel as a target for the therapeutic intervention of vascular diseases.

MiR‐9 promotes angiogenesis of endothelial progenitor cell to facilitate thrombi recanalization via targeting TRPM7 through PI3K/Akt/autophagy pathway

“…Accumulating evidence indicates that TRPM7 is essential for multiple cellular processes, including survival, proliferation and migration in stem cells and endothelial cells via PI3K/Akt pathways . It has been well demonstrated that TRPM7 could inhibit the growth and migration of human umbilical vein endothelial cells (HUVECs) . Instead, inhibited or impaired the expression of TRPM7 could enhance the proliferation and migration, as well as angiogenesis of HUVECs, which might be due to the regulation of NO and the inhibition of autophagy …”

Lipids as central modulators of sensory TRP channels

“…Thus, TRPM7/caveolae/lipid raft association may facilitate TRPM7 scaffolding to cell membrane receptors. Increasing evidence has emerged that TRPM7 negatively regulates the function of vascular endothelial cells and reduced level of TRPM7 might facilitate the vascular repair in case of damage through enhanced angiogenic activity, thus suggesting TRPM7 channel as a target for the therapeutic intervention of vascular diseases [175]. TRPA1 channel is present in cerebral artery endothelial cells and mediates endothelium-dependent dilation in response to oxidized lipid metabolites.…”

Dietary Magnesium and Kidney Function Decline: The Healthy Aging in Neighborhoods of Diversity across the Life Span Study

“…Endothelial cells, layers of which form the endothelial lining of the vasculature, express a magnesium transporter (TRPM7) [45]. Low circulating levels of magnesium may lead to endothelial dysfunction through upregulation of this transporter [45, 46]. Further, hypomagnesemia may impair the healing process following vascular injury by regulating endothelial cell migration and proliferation [47].…”