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Inhibition of human mesangial cell proliferation by targeting T-Type calcium channels

Mulgrew, C.J., A., C.-S., McLatchie, L.M., Brooks, G., Shattock, M.J. and Hendry, B.M. (2009) Inhibition of human mesangial cell proliferation by targeting T-Type calcium channels. Nephron Experimantal Nephrology, 113 (2). e77-e88. ISSN 1660-2129

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To link to this article DOI: 10.1159/000232590

Abstract/Summary

Background: Aberrant glomerular mesangial cell (MC) proliferation is a common finding in renal diseases. T-type calcium channels (T-CaCN) play an important role in the proliferation of a number of cell types, including vascular smooth muscle cells. The hypothesis that T-CaCN may play a role in the proliferation of human MC was investigated. Methods: The presence of T-CaCN in primary cultures of human MC was examined using voltage clamping and by RT-PCR. The effect of calcium channel inhibitors, and of siRNA directed against the Cav3.2 T-CaCN isoform, on MC proliferation was assessed using the microculture tetrazolium assay and nuclear BrdU incorporation. Results: Human MC express only the Cav3.2 T-CaCN isoform. Co-incubation of MC with a T-CaCN inhibitor (mibefradil, TH1177 or Ni2+) results in a concentration-dependent attenuation of proliferation. This effect cannot be attributed to direct drug-induced cytotoxicity or apoptosis and is not seen with verapamil, an L-type channel blocker. Transfection of MC with siRNA results in knockdown of T-CaCN Cav3.2 mRNA and a clear attenuation of MC proliferation. Conclusions: These results demonstrate for the first time an important role for T-CaCN in human MC proliferation. This could potentially lead to a novel therapy in the treatment of proliferative renal diseases.

Item Type:Article
Refereed:Yes
Divisions:Faculty of Life Sciences > School of Chemistry, Food and Pharmacy > School of Pharmacy
Faculty of Life Sciences > School of Biological Sciences
Interdisciplinary centres and themes > Institute for Cardiovascular and Metabolic Research (ICMR)
ID Code:9661
Uncontrolled Keywords:Calcium channel, Glomerulonephritis, Human mesangial cell proliferation, Mesangial cell proliferation, Mesangial cells, Non-excitable cells, T-type calcium channels

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