Abstract
Transient receptor potential vanilloid (TRPV) channels are nonselective cation channels pertinent to diverse physiological functions. Multiple TRPV channel subtypes have been identified in different tissues and cloned. The aim of this study was to investigate the role of TRPV channels in hypoxia-induced proliferation of human pulmonary artery smooth muscle cells (PASMCs) and its possible signal pathway. Reverse transcriptase–polymerase chain reaction, real-time polymerase chain reaction, and Western blot analysis were used to detect the expression of TRPV in human PASMCs. Cell number was determined with a hemocytometer. Cytosolic Ca2+ concentration ([Ca2+]cyt) was measured with a dynamic digital Ca2+ imaging system. The mRNA of TRPV1-4 was detected in human PASMCs and chronic hypoxia up-regulated expression levels of the TRPV1 gene and protein. The ability to proliferate, the resting [Ca2+]cyt, and cyclopiazonic acid–induced capacitative Ca2+ entry in human PASMCs were enhanced significantly by chronic hypoxia compared with the control, and these effects were inhibited in a dose-dependent manner by capsazepine, a TRPV1 channel inhibitor. These results suggest that TRPV1 may be a critical pathway or mediator in chronic hypoxia-induced proliferation of human PASMCs.
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Acknowledgments
This study was supported by the National Science and Technology Pillar Program in the Eleventh Five-year Plan Period (grant 2006BAI01A06), the Natural Science Foundation of Beijing (grant 7082012), the Scientific Research Common Program of Beijing Municipal Commission of Education (grant KM200710025002), the Key Project of Science Foundation of Ministry of Education of China (grant 208002), and the Ministry of Science and Technology of China (grant 2009CB522107).
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Wang, Y.X., Wang, J., Wang, C. et al. Functional Expression of Transient Receptor Potential Vanilloid-Related Channels in Chronically Hypoxic Human Pulmonary Arterial Smooth Muscle Cells. J Membrane Biol 223, 151–159 (2008). https://doi.org/10.1007/s00232-008-9121-9
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DOI: https://doi.org/10.1007/s00232-008-9121-9