{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T05:56:58Z","timestamp":1777960618960,"version":"3.51.4"},"reference-count":72,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,3,28]],"date-time":"2023-03-28T00:00:00Z","timestamp":1679961600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["81873523"],"award-info":[{"award-number":["81873523"]}]},{"name":"National Natural Science Foundation of China","award":["82070490"],"award-info":[{"award-number":["82070490"]}]},{"name":"Hubei Engineering Research Center","award":["81873523"],"award-info":[{"award-number":["81873523"]}]},{"name":"Hubei Engineering Research Center","award":["82070490"],"award-info":[{"award-number":["82070490"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Pulmonary arterial hypertension (PAH) is a group of severe, progressive, and debilitating diseases with limited therapeutic options. This study aimed to explore novel therapeutic targets in PAH through bioinformatics and experiments. Weighted gene co-expression network analysis (WGCNA) was applied to detect gene modules related to PAH, based on the GSE15197, GSE113439, and GSE117261. GSE53408 was applied as validation set. Subsequently, the validated most differentially regulated hub gene was selected for further ex vivo and in vitro assays. PARM1, TSHZ2, and CCDC80 were analyzed as potential intervention targets for PAH. Consistently with the bioinformatic results, our ex vivo and in vitro data indicated that PARM1 expression increased significantly in the lung tissue and\/or pulmonary artery of the MCT-induced PAH rats and hypoxia-induced PAH mice in comparison with the respective controls. Besides, a similar expression pattern of PARM1 was found in the hypoxia- and PDGF--treated isolated rat primary pulmonary arterial smooth muscle cells (PASMCs). In addition, hypoxia\/PDGF--induced PARM1 protein expression could promote the elevation of phosphorylation of AKT, phosphorylation of FOXO3A and PCNA, and finally the proliferation of PASMCs in vitro, whereas PARM1 siRNA treatment inhibited it. Mechanistically, PARM1 promoted PAH via AKT\/FOXO3A\/PCNA signaling pathway-induced PASMC proliferation.<\/jats:p>","DOI":"10.3390\/ijms24076385","type":"journal-article","created":{"date-parts":[[2023,3,29]],"date-time":"2023-03-29T02:03:53Z","timestamp":1680055433000},"page":"6385","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["PARM1 Drives Smooth Muscle Cell Proliferation in Pulmonary Arterial Hypertension via AKT\/FOXO3A Axis"],"prefix":"10.3390","volume":"24","author":[{"given":"Zhen","family":"He","sequence":"first","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"},{"name":"Hubei Provincial Engineering Research Center of Vascular Interventional Therapy, Wuhan 430030, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teding","family":"Chang","sequence":"additional","affiliation":[{"name":"Division of Trauma & Surgical Critical Care, Department of Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"},{"name":"Hubei Provincial Engineering Research Center of Vascular Interventional Therapy, Wuhan 430030, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0169-4257","authenticated-orcid":false,"given":"Hongjie","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"},{"name":"Hubei Provincial Engineering Research Center of Vascular Interventional Therapy, Wuhan 430030, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Dai","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"},{"name":"Hubei Provincial Engineering Research Center of Vascular Interventional Therapy, Wuhan 430030, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hesong","family":"Zeng","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"},{"name":"Hubei Provincial Engineering Research Center of Vascular Interventional Therapy, Wuhan 430030, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1801887","DOI":"10.1183\/13993003.01887-2018","article-title":"Pathology and pathobiology of pulmonary hypertension: State of the art and research perspectives","volume":"53","author":"Humbert","year":"2019","journal-title":"Eur. 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