{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T11:01:18Z","timestamp":1772794878060,"version":"3.50.1"},"reference-count":44,"publisher":"Portland Press Ltd.","issue":"9","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,5,31]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Nuclear receptor binding SET domain 2 (NSD2)-mediated metabolic reprogramming has been demonstrated to regulate oncogenesis via catalyzing the methylation of histones. The present study aimed to investigate the role of NSD2-mediated metabolic abnormality in pulmonary arterial hypertension (PAH). Monocrotaline (MCT)-induced PAH rat model was established and infected with adeno-associated virus carrying short hairpin RNA (shRNA) targeting NSD2. Hemodynamic parameters, ventricular function, and pathology were evaluated by microcatheter, echocardiography, and histological analysis. Metabolomics changes in lung tissue were analyzed by LC\u2013MS. The results showed that silencing of NSD2 effectively ameliorated MCT-induced PAH and right ventricle dysfunction, and partially reversed pathological remodeling of pulmonary artery and right ventricular hypertrophy. In addition, the silencing of NSD2 markedly reduced the di-methylation level of H3K36 (H3K36me2 level) and inhibited autophagy in pulmonary artery. Non-targeted LC\u2013MS based metabolomics analysis indicated that trehalose showed the most significant change in lung tissue. NSD2-regulated trehalose mainly affected ABC transporters, mineral absorption, protein digestion and absorption, metabolic pathways, and aminoacyl-tRNA biosynthesis. In conclusion, we reveal a new role of NSD2 in the pathogenesis of PAH related to the regulation of trehalose metabolism and autophagy via increasing the H3K36me2 level. NSD2 is a promising target for PAH therapy.<\/jats:p>","DOI":"10.1042\/cs20190142","type":"journal-article","created":{"date-parts":[[2019,4,30]],"date-time":"2019-04-30T16:07:46Z","timestamp":1556640466000},"page":"1085-1096","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["NSD2 silencing alleviates pulmonary arterial hypertension by inhibiting trehalose metabolism and autophagy"],"prefix":"10.1042","volume":"133","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2879-2882","authenticated-orcid":false,"given":"Xue-liang","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Cardiac Surgery, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi 330006, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhi-bo","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi 330006, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rong-rong","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Affiliated Hospital of Traditional Chinese and Western Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang 330006, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huang","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi 330006, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qi-rong","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi 330006, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hua","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi 330006, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liang","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi 330006, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yun-yun","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi 330006, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cha-hua","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Cardiovasology, Second Affiliated Hospital, Nanchang University, Nanchang, Jiangxi 330006, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qi-cai","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi 330006, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji-chun","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi 330006, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2019,5,9]]},"reference":[{"key":"2021113012293420200_B1","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1089\/ars.2017.7217","article-title":"Hallmarks of pulmonary hypertension: mesenchymal and inflammatory cell metabolic reprogramming","volume":"28","author":"D\u2019Alessandro","year":"2018","journal-title":"Antioxid. 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