{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T17:33:26Z","timestamp":1787160806986,"version":"build-2736575974"},"reference-count":46,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"16","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2026,8,18]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Pulmonary hypertension is a malignant cardiovascular disease characterized by pulmonary vascular remodeling, with core pathological features including pulmonary arterial wall thickening and elevated pulmonary vascular remodeling due to aberrant proliferation of pulmonary arterial smooth muscle cells (PASMCs). The molecular regulatory mechanisms underlying pulmonary vascular remodeling remain incompletely understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p xml:lang=\"en\">Transcriptome sequencing was employed to screen for differentially expressed genes in lung artery tissues of control and Sugen5416 combined hypoxia\u2010induced rat models. A series of in\u00a0vitro and in\u00a0vivo experiments, including scratch assays, EdU staining, Cell Counting Kit\u20108cell proliferation assays, immunofluorescence, immunoblotting, and overexpression\/knockdown techniques, were performed to investigate the molecular mechanism by which KRT17 (keratin 17) induces PASMCs proliferation and promotes pulmonary hypertension vascular remodeling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">KRT17 was found to be highly expressed in lung tissues of patients with pulmonary hypertension, as well as in pulmonary arterial tissue and hypoxic PASMCs models. Both in\u00a0vivo and in\u00a0vitro experiments demonstrated that KRT17 was a critical regulator of PASMCs proliferation. METTL14 (methyltransferasean14, an m6A methyltransferase complex subunit) was identified as a potential modulator of KRT17 RNA methylation, enhancing its RNA stability and protein expression. Furthermore, KRT17 promoted PASMCs proliferation through upregulation of LCN2 (lipocalin\u20102).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">Our study reveals a novel molecular mechanism by which KRT17 expression is regulated via METTL14\u2010mediated m6A methylation, and further elucidates the role of KRT17 in inducing PASMCs proliferation through the LCN2 signaling pathway. These findings provide significant theoretical insights for the development of innovative therapeutic targets for pulmonary hypertension.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.125.045577","type":"journal-article","created":{"date-parts":[[2026,8,8]],"date-time":"2026-08-08T03:43:37Z","timestamp":1786160617000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Keratin 17 Methyltransferasean14 Methylation Axis: A Novel Mechanism in Pulmonary Vascular Remodeling"],"prefix":"10.1161","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8394-6253","authenticated-orcid":false,"given":"Yun","family":"Liu","sequence":"first","affiliation":[{"name":"The First Affiliated Hospital of Kangda College of Nanjing Medical University;The Affiliated Lianyungang Hospital of Xuzhou Medical University\/The First People\u2019s Hospital of Lianyungang","place":["Lianyungang, China"]},{"name":"Lianyungang Clinical College of Nanjing Medical University; Lianyungang Medical\u2010Education Innovation and Research Center, Nanjing Medical University\/The First People\u2019s Hospital of Lianyungang","place":["Lianyungang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6694-7763","authenticated-orcid":false,"given":"Min","family":"Kong","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Kangda College of Nanjing Medical University;The Affiliated Lianyungang Hospital of Xuzhou Medical University\/The First People\u2019s Hospital of Lianyungang","place":["Lianyungang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Xia","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Kangda College of Nanjing Medical University;The Affiliated Lianyungang Hospital of Xuzhou Medical University\/The First People\u2019s Hospital of Lianyungang","place":["Lianyungang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Chen","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Kangda College of Nanjing Medical University;The Affiliated Lianyungang Hospital of Xuzhou Medical University\/The First People\u2019s Hospital of Lianyungang","place":["Lianyungang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3138-417X","authenticated-orcid":false,"given":"Yanjiao","family":"Jiang","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Kangda College of Nanjing Medical University;The Affiliated Lianyungang Hospital of Xuzhou Medical University\/The First People\u2019s Hospital of Lianyungang","place":["Lianyungang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-7078-1208","authenticated-orcid":false,"given":"Luming","family":"Jin","sequence":"additional","affiliation":[{"name":"Jinzhou Medical University Postgraduate Training Base, The First People's Hospital of Lianyungang","place":["Lianyungang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Wang","sequence":"additional","affiliation":[{"name":"Jinzhou Medical University Postgraduate Training Base, The First People's Hospital of Lianyungang","place":["Lianyungang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyao","family":"Tang","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Kangda College of Nanjing Medical University;The Affiliated Lianyungang Hospital of Xuzhou Medical University\/The First People\u2019s Hospital of Lianyungang","place":["Lianyungang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaochen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Lianyungang Clinical College of Nanjing Medical University; Lianyungang Medical\u2010Education Innovation and Research Center, Nanjing Medical University\/The First People\u2019s Hospital of Lianyungang","place":["Lianyungang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8362-2364","authenticated-orcid":false,"given":"Yi","family":"Xu","sequence":"additional","affiliation":[{"name":"The Affiliated Lianyungang Hospital of Xuzhou Medical University, The First People's Hospital of Lianyungang","place":["Lianyungang, China"]},{"name":"Wuxi Huishan District People's Hospital","place":["Wuxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-023-00486-7"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.18999\/nagjms.81.1.19"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01904-2018.7"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2018.04.003"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2023.103559"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chest.2021.08.040"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/3959845"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2022.12848"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.4161\/rna.28829"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-020-00450-x"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-022-01500-4"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.3892\/or.2021.7987"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41440-024-01607-9"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12265-023-10458-7"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.202011-4185ED"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.722728"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells11071101"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.18632\/aging.202616"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12931-021-01728-6"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23116077"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.envpol.2022.120634"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-22-0814"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1007\/s13258-023-01437-y"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.18632\/aging.203471"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/6176043"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2023.175502"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00204813"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15074"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12551-021-00828-3"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2022.4402"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2022.818416"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.2147\/CMAR.S218926"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.3892\/or.2020.7611"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.21037\/tcr-21-2118"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2020.11469"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.124.069864"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.03.043"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21239222"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.202009-3419OC"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2021.119366"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jprot.2019.103557"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.7150\/jca.90689"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2023.108385"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00380-020-01556-6"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2021.12.011"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.116091"}],"container-title":["Journal of the American Heart Association"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/JAHA.125.045577","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T16:33:28Z","timestamp":1787157208000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/JAHA.125.045577"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,18]]},"references-count":46,"journal-issue":{"issue":"16","published-print":{"date-parts":[[2026,8,18]]}},"alternative-id":["10.1161\/JAHA.125.045577"],"URL":"https:\/\/doi.org\/10.1161\/jaha.125.045577","relation":{},"ISSN":["2047-9980"],"issn-type":[{"value":"2047-9980","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,18]]},"assertion":[{"value":"2025-08-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-19","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e045577"}}