Silencing TRPM7 mimics the effects of magnesium deficiency in human microvascular endothelial cells

Angiogenesis. 2012 Mar;15(1):47-57. doi: 10.1007/s10456-011-9242-0. Epub 2011 Dec 20.

Abstract

Evidence has accumulated to suggest that magnesium might play a role in controlling angiogenesis. Since microvascular endothelial cells are protagonists in this process, we investigated the behavior of these cells cultured in low extracellular magnesium or silenced for its transporter Transient Receptor Potential Melastatin (TRPM)7, essential for cellular magnesium homeostasis. In particular, we focused on some crucial steps of the angiogenic process, i.e. proliferation, migration, protease production and organization in tridimensional structures. Silencing TRPM7 mimics the effects of low extracellular magnesium on human microvascular endothelial cells (HMEC). Indeed, while no effects were observed on the production of metalloproteases and on tridimensional organization on matrigel, both magnesium deficiency and silencing of TRPM7 impair cell migration and inhibit growth by arresting the cells in the G0/G1 and G2/M phases of the cell cycle. Since low extracellular magnesium markedly decreases TRPM7 in HMEC, we suggest that TRPM7 downregulation might mediate low magnesium-induced inhibition of cell growth and migration. Human endothelial cells from the umbilical vein are growth inhibited by low magnesium and growth stimulated after TRPM7 silencing. An impairment of ERK phosphorylation in HMEC silencing TRPM7 is responsible, in part, for the different proliferative behavior of these two cell types. We broadened our studies also to endothelial colony-forming cells and found that they are sensitive to fluctuations of the concentrations of extracellular magnesium, while their proliferation rate is not modulated by TRPM7 silencing. Our results point to magnesium and TRPM7 as a modulators of the angiogenic phenotype of microvascular endothelial cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antioxidants / pharmacology
  • Cell Differentiation / drug effects
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Collagen / pharmacology
  • Colony-Forming Units Assay
  • Culture Media / pharmacology
  • Down-Regulation / drug effects
  • Drug Combinations
  • Endothelial Cells / drug effects
  • Endothelial Cells / enzymology
  • Endothelial Cells / metabolism*
  • Endothelial Cells / pathology
  • Gene Silencing* / drug effects
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Human Umbilical Vein Endothelial Cells / pathology
  • Humans
  • Laminin / pharmacology
  • Magnesium / pharmacology
  • Magnesium Deficiency / metabolism*
  • Magnesium Deficiency / pathology
  • Matrix Metalloproteinases / metabolism
  • Microvessels / pathology*
  • Protein-Serine-Threonine Kinases
  • Proteoglycans / pharmacology
  • TRPM Cation Channels / genetics*
  • TRPM Cation Channels / metabolism

Substances

  • Antioxidants
  • Culture Media
  • Drug Combinations
  • Laminin
  • Proteoglycans
  • TRPM Cation Channels
  • matrigel
  • Collagen
  • Protein-Serine-Threonine Kinases
  • TRPM7 protein, human
  • Matrix Metalloproteinases
  • Magnesium