title: Silencing TRPM7 promotes growth/proliferation and nitric oxide production of vascular endothelial cells via the ERK pathway.
abstract: OBJECTIVE
  The presence and potential function of transient receptor potential melastatin 7 (TRPM7), a Ca2+-permeable non-selective cation channel of the TRP channel superfamily in human vascular endothelial cells, were examined.
  
  
  RESULTS
  Whole-cell patch-clamp recordings showed outward-rectifying currents in human umbilical vein endothelial cells (HUVECs), which was potentiated by removing the extracellular Ca2+ and Mg2+, but inhibited by non-specific TRPM7 blocker Gd3+ or 2-aminoethoxydiphenyl borate (2-APB). TRPM7 mRNA was detected in HUVECs by RT-PCR, but TRPM6, its closest homologue, was not. Silencing TRPM7 by small interfering RNA (siRNA) decreased the level of TRPM7 mRNA and the TRPM7-like current. Interestingly, knockdown of TRPM7 with siRNA or inhibition of TRPM7 function with 2-APB increased the phosphorylation of extracellular signal-regulated kinase (ERK) and enhanced growth/proliferation of HUVECs. This enhanced cell growth/proliferation was abolished by an inhibitor of the ERK signalling pathway. In addition to cell growth/proliferation, silencing TRPM7 also increased expression of nitric oxide synthase and nitric oxide production in an ERK pathway-dependent manner.
  
  
  CONCLUSIONS
  These observations suggest that TRPM7 channels may play an important role in the function of vascular endothelial cells.
authors.affiliation: Robert S. Dow Neurobiology Laboratories, Legacy Research, 1225 NE 2nd Ave. Portland, OR 97232, USA.
authors.forename: Koichi
authors.initials: K
authors.lastname: Inoue
authors.forename: Zhi-Gang
authors.initials: ZG
authors.lastname: Xiong
mesh_terms: D001896:Boron Compounds / Q000494:pharmacology; D002070:Butadienes / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects / Q000201:enzymology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008274:Magnesium / Q000378:metabolism; D008564:Membrane Potentials; D049990:Membrane Transport Modulators / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D050053:TRPM Cation Channels / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D001896:Boron Compounds; D002070:Butadienes; D049990:Membrane Transport Modulators; D009570:Nitriles; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D050053:TRPM Cation Channels; C113580:U 0126; D009569:Nitric Oxide; C109986:2-aminoethoxydiphenyl borate; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D017346:Protein Serine-Threonine Kinases; C486583:TRPM7 protein, human; D048049:Extracellular Signal-Regulated MAP Kinases; D008274:Magnesium; D002118:Calcium