title: SENP‑1 enhances hypoxia‑induced proliferation of rat pulmonary artery smooth muscle cells by regulating hypoxia‑inducible factor‑1α.
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.
authors.affiliation: Department of Respiratory Medicine, Hunan Institute of Gerontology, Hunan Province Geriatric Hospital, Changsha, Hunan 410016, P.R. China.
authors.forename: Fang
authors.initials: F
authors.lastname: Zhou
authors.affiliation: Department of Respiratory Medicine, Hunan Institute of Gerontology, Hunan Province Geriatric Hospital, Changsha, Hunan 410016, P.R. China.
authors.forename: Aiguo
authors.initials: A
authors.lastname: Dai
authors.affiliation: Department of Respiratory Medicine, Hunan Institute of Gerontology, Hunan Province Geriatric Hospital, Changsha, Hunan 410016, P.R. China.
authors.forename: Yongliang
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Respiratory Medicine, The Second Affiliated Hospital of University of South China, Hengyang, Hunan 421001, P.R. China.
authors.forename: Xiaowu
authors.initials: X
authors.lastname: Tan
authors.affiliation: Department of Respiratory Medicine, The Second Affiliated Hospital of University of South China, Hengyang, Hunan 421001, P.R. China.
authors.forename: Xiufeng
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D015687:Cell Hypoxia; D049109:Cell Proliferation; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases; D010450:Endopeptidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D008297:Male; D008856:Microscopy, Fluorescence; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism; D011651:Pulmonary Artery / Q000166:cytology; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D042461:Vascular Endothelial Growth Factor A; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; C000630128:SENP1 protein, rat