5-HT promotes pulmonary arterial smooth muscle cell proliferation through the TRPC channel.
CELLULAR AND MOLECULAR BIOLOGY(2018)
摘要
Pulmonary arterial hypertension is caused by an imbalance of pulmonary vasoconstriction and vasodilation. Pulmonary arteriolar remodeling is a primary pathological change and proliferation of pulmonary arterial smooth muscle cells (PASMC) is an important pathological basis for pulmonary arteriolar remodeling. Vasoactive substances, such as 5-HT, may play a role in proliferation of PASMC via unknown mechanisms. In vitro experiments with PASMC showed that the TRPC channel inhibitor SKF96365 inhibited the effects 5-HT and DOI on PASMC proliferation and G2M percentage increase, and decreased expression of TRPC1, TRPC6 and calcineurin A/NFATc3 induced by 5-HT and DOI. SKF96365 inhibited binding of NFATc3 and DNA promoted by 5-HT and DOI. Therefore, 5-HT may affect the TRPC channel to promote proliferation of PASMC; upregulate expression of TRPC1, TRPC6, and calcineurin A/NFATc3; and therefore promote NFATc3 nuclear translocation. There may be crosstalk between 5-HT and TRPC, which may contribute to the pathogeneis of pulmonary arterial hypertension and this may be a novel therapeutic target for treating pulmonary arterial hypertension.
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关键词
Pulmonary arterial hypertension,5-HT,TRPC channel,Cell proliferation,NFAT
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