{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T07:49:10Z","timestamp":1789631350243,"version":"build-2803163510"},"reference-count":57,"publisher":"American Society for Clinical Investigation","issue":"10","license":[{"start":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T00:00:00Z","timestamp":1747872000000},"content-version":"vor","delay-in-days":35,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"crossref","award":["GNT1158998"],"award-info":[{"award-number":["GNT1158998"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"crossref"}]},{"name":"NSW Cardiovascular Health Grant","award":["RG201832"],"award-info":[{"award-number":["RG201832"]}]},{"name":"Heart Foundation Future Leader Fellowship","award":["101856"],"award-info":[{"award-number":["101856"]}]},{"name":"NSW Cardiovascular Health Grant","award":["46014"],"award-info":[{"award-number":["46014"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,5,22]]},"abstract":"<jats:p>\n                    Vascular smooth muscle cells (VSMCs) possess significant phenotypic plasticity, shifting between a contractile phenotype and a synthetic state for vascular repair\/remodeling. Dysregulated VSMC transformation, marked by excessive proliferation and migration, primarily drives intimal hyperplasia.\n                    <jats:italic>N<\/jats:italic>\n                    <jats:sup>6<\/jats:sup>\n                    -methyladenosine (m\n                    <jats:sup>6<\/jats:sup>\n                    A), the most prevalent RNA modification in eukaryotes, plays a critical role in gene expression regulation; however, its impact on VSMC plasticity is not fully understood. We investigated the changes in m\n                    <jats:sup>6<\/jats:sup>\n                    A modification and its regulatory factors during VSMC phenotypic shifts and their influence on intimal hyperplasia. We demonstrate that METTL14, crucial for m\n                    <jats:sup>6<\/jats:sup>\n                    A deposition, significantly promoted VSMC dedifferentiation. METTL14 expression, initially negligible, was elevated in synthetic VSMC cultures, postinjury neointimal VSMCs, and human restenotic arteries. Reducing Mettl14 levels in mouse primary VSMCs decreased prosynthetic genes, suppressing their proliferation and migration. m\n                    <jats:sup>6<\/jats:sup>\n                    A-RIP-seq profiling showed key VSMC gene networks undergo altered m\n                    <jats:sup>6<\/jats:sup>\n                    A regulation in Mettl14-deficient cells. Mettl14 enhanced Klf4 and Serpine1 expression through increased m\n                    <jats:sup>6<\/jats:sup>\n                    A deposition. Local Mettl14 knockdown significantly curbed neointimal formation after arterial injury, and reducing Mettl14 in hyperplastic arteries halted further neointimal development. We show that Mettl14 is a pivotal regulator of VSMC dedifferentiation, influencing Klf4- and Serpine1-mediated phenotypic conversion. Inhibiting METTL14 is a viable strategy for preventing restenosis and halting restenotic occlusions.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.184444","type":"journal-article","created":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T12:50:36Z","timestamp":1745412636000},"source":"Crossref","is-referenced-by-count":6,"title":["METTL14 promotes intimal hyperplasia through m6A-mediated control of vascular smooth muscle dedifferentiation genes"],"prefix":"10.1172","volume":"10","author":[{"given":"Grace","family":"Chensee","sequence":"first","affiliation":[{"name":"Vascular Epigenetics Laboratory, Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bob S.L.","family":"Lee","sequence":"additional","affiliation":[{"name":"Vascular Epigenetics Laboratory, Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales, Australia."},{"name":"School of Clinical Medicine, Faculty of Medicine and Health, University of New South Wales, Sydney, New South Wales, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Immanuel D.","family":"Green","sequence":"additional","affiliation":[{"name":"Epigenetics and RNA Biology Laboratory, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, New South Wales, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Tieng","sequence":"additional","affiliation":[{"name":"Epigenetics and RNA Biology Laboratory, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, New South Wales, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8228-7281","authenticated-orcid":true,"given":"Renhua","family":"Song","sequence":"additional","affiliation":[{"name":"Epigenetics and RNA Biology Laboratory, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, New South Wales, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Pinello","sequence":"additional","affiliation":[{"name":"Epigenetics and RNA Biology Laboratory, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, New South Wales, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quintin","family":"Lee","sequence":"additional","affiliation":[{"name":"Epigenetics and RNA Biology Laboratory, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, New South Wales, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Majid","family":"Mehravar","sequence":"additional","affiliation":[{"name":"Epigenetics and RNA Biology Laboratory, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, New South Wales, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Robinson","sequence":"additional","affiliation":[{"name":"Royal Prince Alfred Hospital, Sydney, New South Wales, Australia."},{"name":"Centre for Peripheral Artery Disease, Heart Research Institute, Newtown, New South Wales, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mian","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery, National Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, the First Affiliated Hospital for Sun Yat-Sen University, Guangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary M.","family":"Kavurma","sequence":"additional","affiliation":[{"name":"Centre for Peripheral Artery Disease, Heart Research Institute, Newtown, New South Wales, Australia."},{"name":"School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, New South Wales, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Yu","sequence":"additional","affiliation":[{"name":"Center for Metabolic Disease Research and Department of Cardiovascular Sciences, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin J.L.","family":"Wong","sequence":"additional","affiliation":[{"name":"Epigenetics and RNA Biology Laboratory, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, New South Wales, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renjing","family":"Liu","sequence":"additional","affiliation":[{"name":"Vascular Epigenetics Laboratory, Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales, Australia."},{"name":"School of Clinical Medicine, Faculty of Medicine and Health, University of New South Wales, Sydney, New South Wales, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2025,4,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2022.05.017"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagrm.2014.06.004"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.120.050553"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00041.2003"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/nature02382"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M412862200"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.25.1.364-376.2005"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.113.002887"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1172\/JCI26505"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.02.059"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.118.033794"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2017.11.016"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1126\/science.aau1646"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1038\/nature11112"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1038\/nature12730"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.05.014"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-019-0168-5"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1111\/cpr.13386"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2020.592550"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2020.109935"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2022.913039"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-024-05304-1"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/0021-9150(95)05742-0"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2005.08.002"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.05.003"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.2006092"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.116.308344"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.05.012"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-022-01173-1"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1126\/science.aay6018"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehab140"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.93.12.2178"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-019-0089-9"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-018-0174-4"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-34434-y"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.121.316180"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2020.07.022"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.122.318451"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2021.627380"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2019.117034"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1093\/procel\/pwad009"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2014.02.029"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.20.2.335"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.3390\/ijms242417136"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1002\/jbio.201800053"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(97)00109-0"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrep.2021.100916"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.117.310692"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.21769\/BioProtoc.3072"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2021.07.024"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts635"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btt656"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2008-9-9-r137"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btq033"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2010.05.004"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1089\/omi.2011.0118"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/184444\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T17:40:21Z","timestamp":1779126021000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/184444"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,17]]},"references-count":57,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,4,15]]},"published-print":{"date-parts":[[2025,5,22]]}},"alternative-id":["10.1172\/jci.insight.184444"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.184444","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,17]]},"article-number":"e184444"}}