SENP‑1 enhances hypoxia‑induced proliferation of rat pulmonary artery smooth muscle cells by regulating hypoxia‑inducible factor‑1α

Zhou,Fang; Dai,Aiguo; Jiang,Yongliang; Tan,Xiaowu; Zhang,Xiufeng

doi:10.3892/mmr.2016.4969

SENP‑1 enhances hypoxia‑induced proliferation of rat pulmonary artery smooth muscle cells by regulating hypoxia‑inducible factor‑1α

Authors:
- Fang Zhou
- Aiguo Dai
- Yongliang Jiang
- Xiaowu Tan
- Xiufeng Zhang
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Affiliations: Department of Respiratory Medicine, Hunan Institute of Gerontology, Hunan Province Geriatric Hospital, Changsha, Hunan 410016, P.R. China, Department of Respiratory Medicine, The Second Affiliated Hospital of University of South China, Hengyang, Hunan 421001, P.R. China
Published online on: March 3, 2016 https://doi.org/10.3892/mmr.2016.4969
Pages: 3482-3490
Copyright: © Zhou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Hypoxic pulmonary vascular remodeling (HPSR) has an important role in the development of hypoxic pulmonary hypertension. HPSR is predominantly mediated by the proliferation of pulmonary artery smooth muscle cells (PASMCs). Our previous study demonstrated that hypoxia‑inducible factor (HIF)‑1α was able to promote the proliferation of PASMCs. Small ubiquitin‑like modifier (SUMO)ylation is a post‑translational modification that is important in various cellular processes. It has previously been demonstrated that HIF‑1α may be SUMOylated by SUMO. Conversely, SUMO‑specific protease 1 (SENP‑1) was able to increase the stability of HIF‑1α by decreasing SUMOylation of HIF‑1α. In order to investigate whether SUMOylation of HIF‑1α has a role in the proliferation of PASMCs, the present study cultured PASMCs in hypoxic and normoxic chambers in vitro. The proliferation ability of PASMCs was measured using the Cell Counting kit‑8 and 5‑ethynyl‑2'‑deoxyuridine cell proliferation assays. In addition, short hairpin RNA lentiviral particles were used to knockdown the expression of SENP‑1, and the expression levels of HIF‑1α, SENP‑1 and vascular endothelial growth factor (VEGF) were detected at the mRNA and protein levels using semi‑quantitative polymerase chain reaction and western blotting, respectively. The present study demonstrated that SENP‑1 was able to enhance the proliferative ability of PASMCs by initiating deSUMOylation of HIF‑1α and increasing the expression of its downstream responsive gene, VEGF.

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