{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T05:48:54Z","timestamp":1777700934363,"version":"3.51.4"},"reference-count":30,"publisher":"IMR Press","issue":"4","license":[{"start":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T00:00:00Z","timestamp":1776124800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82500082"],"award-info":[{"award-number":["82500082"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"\u201cEstablishment of the Coronary Heart Disease Interventional Diagnosis and Treatment Center at the Cixi Integrated Traditional Chinese and Western Medicine Medical Health Group\u201d","award":["812410050"],"award-info":[{"award-number":["812410050"]}]},{"name":"\u201cThe Role of Leukocyte-Derived Chemokine 2 in Regulating Macrophage Polarization\u201d","award":["882500370"],"award-info":[{"award-number":["882500370"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Front. Biosci. (Landmark Ed)"],"abstract":"<jats:p>Background: Pulmonary hypertension (PH) is a progressive disease characterized by obstructive pulmonary vascular remodeling, for which no curative therapies effectively reverse disease progression. This study investigated whether N-myc downstream-regulated gene 2 (NDRG2) drives PH pathogenesis by regulating mitochondrial dynamics. Methods: NDRG2 expression was examined in two rat models of PH (SuHx and MCT). Functional studies using NDRG2 knockdown and overexpression in PASMCs assessed phenotypic switching, proliferation, migration, mitochondrial morphology, and bioenergetics. The NDRG2-DRP1 interaction was investigated via co-immunoprecipitation and immunofluorescence. An in vivo rescue experiment was performed using intratracheal AAV9-shNDRG2 delivery in SuHx rats. Results: NDRG2 was significantly upregulated in PASMCs from PH rats, hypoxic human PASMCs, and patients with PH. NDRG2 knockdown attenuated, while its overexpression exacerbated, hypoxia-induced phenotypic switching, proliferation, and migration of PASMCs. Mechanistically, NDRG2 directly interacted with DRP1 and specifically promoted its activating phosphorylation at Ser616, leading to excessive mitochondrial fission, ATP depletion, and oxidative stress. These pathogenic effects were abolished by concurrent DRP1 knockdown. In vivo, NDRG2 knockdown ameliorated hemodynamic indices, right ventricular hypertrophy, pulmonary vascular remodeling, and exercise capacity in SuHx rats. Conclusions: NDRG2 drives PH progression by promoting DRP1-mediated mitochondrial fission and vascular remodeling. The NDRG2-DRP1 axis represents a candidate pathway for therapeutic exploration in PH.<\/jats:p>","DOI":"10.31083\/fbl48054","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T09:29:27Z","timestamp":1777454967000},"source":"Crossref","is-referenced-by-count":0,"title":["NDRG2 Drives DRP1 Phosphorylation to Promote the Progression of Pulmonary Hypertension"],"prefix":"10.31083","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-9192-3205","authenticated-orcid":true,"given":"Jiayong","family":"Luo","sequence":"first","affiliation":[{"name":"Department of Cardiology, The First Affiliated Hospital of Ningbo University, 315010 Ningbo, Zhejiang, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4297-9869","authenticated-orcid":true,"given":"Jinyu","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Respiratory Disease, The First Affiliated Hospital, Jinzhou Medical University, 121000 Jinzhou, Liaoning, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-9936-5118","authenticated-orcid":true,"given":"Yi","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The First Affiliated Hospital of Ningbo University, 315010 Ningbo, Zhejiang, China"},{"name":"Department of Respiratory Disease, The First Affiliated Hospital, Jinzhou Medical University, 121000 Jinzhou, Liaoning, China"},{"name":"Institute of One Health Science, School of Civil & Environmental Engineering and Geography Science, State Key Laboratory for Quality and Safety of Agro-products, Ningbo University, 315211 Ningbo, Zhejiang, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-1035-9216","authenticated-orcid":true,"given":"Yusang","family":"Shao","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The First Affiliated Hospital of Ningbo University, 315010 Ningbo, Zhejiang, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1731-0716","authenticated-orcid":true,"given":"Yanyan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The First Affiliated Hospital of Ningbo University, 315010 Ningbo, Zhejiang, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5784-4197","authenticated-orcid":true,"given":"Yingru","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Respiratory Disease, The First Affiliated Hospital, Jinzhou Medical University, 121000 Jinzhou, Liaoning, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-1868-0686","authenticated-orcid":true,"given":"Enfang","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Respiratory Disease, The First Affiliated Hospital, Jinzhou Medical University, 121000 Jinzhou, Liaoning, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3958-654X","authenticated-orcid":true,"given":"Yanqing","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The First Affiliated Hospital of Ningbo University, 315010 Ningbo, Zhejiang, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-8020-3196","authenticated-orcid":true,"given":"Shuangshuang","family":"Tu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The First Affiliated Hospital of Ningbo University, 315010 Ningbo, Zhejiang, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2844-4511","authenticated-orcid":true,"given":"Haoxuan","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The First Affiliated Hospital of Ningbo University, 315010 Ningbo, Zhejiang, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6018-437X","authenticated-orcid":true,"given":"Wenming","family":"He","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The First Affiliated Hospital of Ningbo University, 315010 Ningbo, Zhejiang, China"},{"name":"Institute of One Health Science, School of Civil & Environmental Engineering and Geography Science, State Key Laboratory for Quality and Safety of Agro-products, Ningbo University, 315211 Ningbo, Zhejiang, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"16242","published-online":{"date-parts":[[2026,4,14]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","unstructured":"Adu-Amankwaah J, Shi Y, Song H, Ma Y, Liu J, Wang H, et al. 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