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Cardiovascular Research Advance Access first published online on May 18, 2009
This version [Corrected Proof] published online on June 10, 2009

Cardiovascular Research, doi:10.1093/cvr/cvp153
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2009. For permissions please email: journals.permissions@oxfordjournals.org.

Silencing TRPM7 promotes growth/proliferation and nitric oxide production of vascular endothelial cells via the ERK pathway

Koichi Inoue and Zhi-Gang Xiong*

Robert S. Dow Neurobiology Laboratories, Legacy Research, 1225 NE 2nd Ave. Portland, OR 97232, USA

* Corresponding author. Tel: + 1 503 413 2086; fax: +1 503 413 5465. E-mail address: 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 (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.

Conclusion: 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


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