PDGF mediates pulmonary arterial smooth muscle cell proliferation and migration by regulating NFATc2

Zhao,Fang-Yun; Xu,Shuang-Lan; Zhang,Chun-Fang; Liu,Jie; Zhang,Yue; Yang,Jiao; Xing,Xi-Qian

doi:10.3892/mmr.2020.11677

PDGF mediates pulmonary arterial smooth muscle cell proliferation and migration by regulating NFATc2

Authors:
- Fang-Yun Zhao
- Shuang-Lan Xu
- Chun-Fang Zhang
- Jie Liu
- Yue Zhang
- Jiao Yang
- Xi-Qian Xing
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Affiliations: Department of Pharmacy, Yan'an Hospital Affiliated to Kunming Medical University, Kunming, Yunnan 650051, P.R. China, Department of Respiratory Medicine, The Fourth Affiliated Hospital of Kunming Medical University, The Second People's Hospital of Yunnan Province, Kunming, Yunnan 650021, P.R. China, Department of Geriatrics, The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212000, P.R. China, First Department of Respiratory Medicine, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, P.R. China
Published online on: November 10, 2020 https://doi.org/10.3892/mmr.2020.11677
Article Number: 39
Copyright: © Zhao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The reconstruction of pulmonary vascular structure caused by the proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs) is the central link in the formation of pulmonary arterial hypertension (PAH). Platelet‑derived growth factor (PDGF) can regulate the proliferation and migration of PASMCs. At the same time, nuclear factor of activated T cells (NFATs) plays an important role in the development of PAH. To the best of our knowledge, there are no reports yet regarding whether PDGF regulates NFATc2 to increase the proliferation of PASMCs. The present study aimed to investigate whether PDGF affects the proliferation and migration of PASMCs by regulating NFAT, and to study the pathogenesis of PAH. PASMCs were treated with recombinant PDGF; Cell Counting Kit‑8 and clone formation experiments showed that PDGF enhanced the cell viability and proliferation of PASMCs. Cell cycle distribution and molecular markers related to cell proliferation (cyclin D1, CDK4 and Proliferating Cell Nuclear Antigen) were detected by flow cytometry, and the results indicated that PDGF promoted the division of PAMSCs. The scratch migration and Transwell migration assays showed that the migratory ability of PASMCs was enhanced following PDGF treatment. Changes in NFATs (NFATc1‑5) after PDGF treatment were evaluated by reverse transcription‑quantitative PCR and western blotting; NFATc2 showed the most significant results. Finally, PDGF‑treated cells were treated with an NFAT pathway inhibitor, cyclosporin A, or a small interfering RNA targeting NFATc2, and changes in cell proliferation and migration were evaluated to assess the role of NFATc2 in PDGF‑induced cell proliferation and migration. In conclusion, PDGF may regulate PASMC proliferation and migration by regulating the expression of NFAT, further leading to the occurrence of PAH. It is proposed that NFATc2 could be used as a potential target for PAH treatment.

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