Cardiovascular Research Advance Access [Accepted Manuscript] published online on May 18, 2009
Cardiovascular Research, doi:10.1093/cvr/cvp153
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Silencing TRPM7 promotes growth/proliferation and nitric oxide production of vascular endothelial cells via the ERK pathway
Robert S. Dow Neurobiology Laboratories, Legacy Research, Portland, OR 97232
* Correspondence author: Zhi-Gang Xiong, MD, PhD, Robert S. Dow Neurobiology Laboratories, Legacy Clinical Research Center, 1225 NE 2nd Ave., Portland, OR 97232, Tel. (503) 4132086, Fax. (503) 4135465, E-mail: zxiong{at}Downeurobiology.org
Aims: 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.
Methods and 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. TRPM7 mRNA was detected in HUVECs by RT-PCR, but TRPM6, its closest homologue, was not. Silencing TRPM7 by 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 signaling 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.
KEYWORDS TRPM7; vascular endothelial cells; MAPK; growth/proliferation
Time for primary review: 44 Days