{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T12:29:19Z","timestamp":1780576159896,"version":"3.54.1"},"reference-count":30,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,1,22]],"date-time":"2025-01-22T00:00:00Z","timestamp":1737504000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health","award":["HL117247"],"award-info":[{"award-number":["HL117247"]}]},{"name":"National Institutes of Health","award":["HL119053"],"award-info":[{"award-number":["HL119053"]}]},{"name":"National Institutes of Health","award":["HL147313"],"award-info":[{"award-number":["HL147313"]}]},{"name":"National Institutes of Health","award":["HL151444"],"award-info":[{"award-number":["HL151444"]}]},{"name":"National Institutes of Health","award":["HL173025"],"award-info":[{"award-number":["HL173025"]}]},{"name":"National Institutes of Health","award":["I01 BX006161"],"award-info":[{"award-number":["I01 BX006161"]}]},{"DOI":"10.13039\/100000738","name":"Department of Veterans Affairs Merit Review Awards","doi-asserted-by":"publisher","award":["HL117247"],"award-info":[{"award-number":["HL117247"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"Department of Veterans Affairs Merit Review Awards","doi-asserted-by":"publisher","award":["HL119053"],"award-info":[{"award-number":["HL119053"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"Department of Veterans Affairs Merit Review Awards","doi-asserted-by":"publisher","award":["HL147313"],"award-info":[{"award-number":["HL147313"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"Department of Veterans Affairs Merit Review Awards","doi-asserted-by":"publisher","award":["HL151444"],"award-info":[{"award-number":["HL151444"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"Department of Veterans Affairs Merit Review Awards","doi-asserted-by":"publisher","award":["HL173025"],"award-info":[{"award-number":["HL173025"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"Department of Veterans Affairs Merit Review Awards","doi-asserted-by":"publisher","award":["I01 BX006161"],"award-info":[{"award-number":["I01 BX006161"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Smooth muscle cell (SMC) phenotypic transition contributes to several major vascular diseases such as intimal hyperplasia and restenosis, atherosclerosis, and aneurysm. However, the molecular mechanisms underlying this process are not fully understood. The objectives of this study are to determine the role of mRNA N6-methyladenosine (m6A) modification in SMC phenotypic modulation and injury-induced neointima formation. By using an m6A quantification kit, we found that m6A levels are altered during the early stage of SMC phenotypic modulation. RNA sequencing revealed that m6A modifications in the mRNAs of 708 genes are elevated while modifications in the mRNAs of 300 genes are decreased. These modifications occur in genes widely distributed in most chromosomes and involved in many cellular processes and signaling\/gene regulations. Meanwhile, the regulators for m6A modifications are altered by PDGF-BB, a known factor inducing SMC phenotypic modulation. Although m6A writers and erasers are not altered during SMC phenotypic modulation, m6A reader YTHDF1 is dramatically reduced as early as 12 h following PDGF-BB treatment, a time much earlier than the downregulation of SMC contractile proteins. Importantly, the overexpression of YTHDF1 reverses the expression of SMC contractile proteins, suggesting a restoration of contractile SMC phenotype. By using a rat carotid artery balloon-injury model, we found that injury significantly decreases YTHDF1 levels in the medial SMCs while inducing neointima formation. Of significance, restoring YTHDF1 expression through lentiviral transduction blocks injury-induced neointima formation. Moreover, YTHDF1 delivery restores the expression of SMC contractile proteins that is diminished in arterial media layers due to the injury. These data demonstrate that YTHDF1 plays a protective role in maintaining the contractile SMC phenotype and vascular homeostasis during injury-induced pathological vascular remodeling.<\/jats:p>","DOI":"10.3390\/cells14030160","type":"journal-article","created":{"date-parts":[[2025,1,22]],"date-time":"2025-01-22T03:40:17Z","timestamp":1737517217000},"page":"160","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["YTH N6-methyladenosine RNA Binding Protein 1 Inhibits Smooth Muscle Cell Phenotypic Modulation and Neointimal Hyperplasia"],"prefix":"10.3390","volume":"14","author":[{"given":"Kai","family":"Tian","sequence":"first","affiliation":[{"name":"Department of Surgery, School of Medicine, University of Missouri, Columbia, MO 65212, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dunpeng","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Surgery, School of Medicine, University of Missouri, Columbia, MO 65212, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Physiology & Pharmacology, University of Georgia, Athens, GA 30602, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Surgery, School of Medicine, University of Missouri, Columbia, MO 65212, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4677-4653","authenticated-orcid":false,"given":"Xiaohan","family":"Mei","sequence":"additional","affiliation":[{"name":"Department of Surgery, School of Medicine, University of Missouri, Columbia, MO 65212, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0297-8649","authenticated-orcid":false,"given":"Shi-You","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Surgery, School of Medicine, University of Missouri, Columbia, MO 65212, USA"},{"name":"Department of Physiology & Pharmacology, University of Georgia, Athens, GA 30602, USA"},{"name":"The Research Service, Harry S. Truman Memorial Veterans Hospital, Columbia, MO 65201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e247","DOI":"10.1161\/ATVBAHA.119.312581","article-title":"Smooth Muscle Cells in Vascular Remodeling","volume":"39","author":"Shi","year":"2019","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1784","DOI":"10.1161\/ATVBAHA.111.243212","article-title":"Smooth Muscle Phenotypic Modulation\u2014A Personal Experience","volume":"32","author":"Campbell","year":"2012","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.jvssci.2021.04.001","article-title":"Targeting smooth muscle cell phenotypic switching in vascular disease","volume":"2","author":"Chakraborty","year":"2021","journal-title":"JVS-Vasc. 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