TMEM16A regulates the cell cycle of pulmonary artery smooth muscle cells in high‑flow‑induced pulmonary arterial hypertension rat model

Shang,Lifeng; Wang,Kai; Liu,Dongli; Qin,Suyuan; Huang,Jinglin; Zhao,Yijue; Pang,Yusheng

doi:10.3892/etm.2020.8589

TMEM16A regulates the cell cycle of pulmonary artery smooth muscle cells in high‑flow‑induced pulmonary arterial hypertension rat model

Authors:
- Lifeng Shang
- Kai Wang
- Dongli Liu
- Suyuan Qin
- Jinglin Huang
- Yijue Zhao
- Yusheng Pang
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Affiliations: Department of Pediatrics, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guanxi 530021, P.R. China, Department of Pediatrics, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China
Published online on: March 9, 2020 https://doi.org/10.3892/etm.2020.8589
Pages: 3275-3281
Copyright: © Shang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

High‑flow‑induced pulmonary arterial hypertension (PAH) has attained global notoriety, the mechanism of which remains elusive. The present study investigated the regulation of Anoctamin‑1, also known as transmembrane member 16A (TMEM16A), in the cell cycle progression of pulmonary artery smooth muscle cells (PASMCs) from a PAH rat model induced by high pulmonary blood flow. A total of 30 Sprague‑Dawley rats were randomly assigned into control, sham and shunt groups. A rat model of high pulmonary blood flow‑induced PAH was established by surgery using abdominal aorta‑inferior vena cava fistula. Right ventricular pressure, right ventricular hypertrophy index and pulmonary arteriole structural remodeling were assessed 11 weeks following operation. The cell cycle statuses of PASMCs was assessed via flow cytometry, whereas western blot analysis was performed to measure the expression of cyclin D1, CDK2, p27KIP and cyclin E in primary PASMCs isolated from rats. The expression of cyclin E and cyclin D1 was revealed to be increased in the shunt group compared with the control group, which was accompanied with an increased expression of TMEM16A in the shunt group. Changes in the ratio of PASMCs in the G0/G1, S and G2/M phases of cycle induced by PAH were reversed by TMEM16A knockdown. The expression of cyclin E and cyclin D1 in the shunt group was significantly higher compared with the control group in vitro, which was reversed by TMEM16A‑siRNA transfection. In conclusion, TMEM16A may be involved in high pulmonary blood flow‑induced PAH by regulating PASMC cell cycle progression.

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