TRPC6 is required for hypoxia‑induced basal intracellular calcium concentration elevation, and for the proliferation and migration of rat distal pulmonary venous smooth muscle cells

Wang,Qingjie; Wang,Dong; Yan,Gaoling; Sun,Ling; Tang,Chengchun

doi:10.3892/mmr.2015.4750

TRPC6 is required for hypoxia‑induced basal intracellular calcium concentration elevation, and for the proliferation and migration of rat distal pulmonary venous smooth muscle cells

Authors:
- Qingjie Wang
- Dong Wang
- Gaoling Yan
- Ling Sun
- Chengchun Tang
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Affiliations: Department of Cardiology, Zhongda Hospital of Southeast University, Nanjing, Jiangsu 210009, P.R. China, Department of Cardiology, Changzhou Hospital of Nanjing Medical University, Changzhou, Jiangsu 213000, P.R. China
Published online on: December 30, 2015 https://doi.org/10.3892/mmr.2015.4750
Pages: 1577-1585
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Hypoxia induces pulmonary vasoconstriction and reconstruction in the pulmonary arteries and pulmonary veins (PVs), and elevation of intracellular calcium concentration ([Ca2+]i) is a primary factor of these processes. In the present study, the role of transient receptor potential cation channels (TRPCs) in mediating the hypoxia‑induced elevation of [Ca2+]i in rat distal pulmonary venous smooth muscle cells (PVSMCs) was investigated. Rats with chronic hypoxic pulmonary hypertension (CHPH) were used for in vivo experiments, and PVSMCs were isolated for in vitro experiments. [Ca2+]i was measured using fura‑2‑based fluorescence calcium imaging. Reverse transcription‑quantitative polymerase chain reaction and western blotting were used to detect the mRNA and protein expression levels of TRPCs. Methyl thiazolyl tetrazolium and Transwell assays were used to investigate the proliferation and migration of PVSMCs, respectively. The results of the present study demonstrated that TRPC6 was increased in the distal PVs of CHPH rats, and in PVSMCs exposed to hypoxic conditions (4% O2, 72 h); however, TRPC1 was not. The 1‑oleoyl-2‑acetyl-sn-glycerol-induced [Ca2+]i elevation was increased in PVSMCs isolated from CHPH rats and in PVSMCs cultured under hypoxic conditions (4% O2, 72 h). Hypoxia induced PVSMC [Ca2+]i elevation, proliferation and migration. These alterations were inhibited following TRPC6 knockdown. Results from the present study suggest that TRPC6 expression is increased during chronic hypoxia, which contributes to Ca2+ entry into the cell, thus promoting proliferation and migration of PVSMCs.

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