{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T11:29:25Z","timestamp":1788866965026,"version":"build-2803163510"},"reference-count":38,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:sec>\n            <jats:title>BACKGROUND:<\/jats:title>\n            <jats:p>\n              Vascular smooth muscle cell (VSMC) migration and proliferation substantially contribute to neointimal hyperplasia related to in-stent restenosis. N\n              <jats:sup>6<\/jats:sup>\n              -methyladenosine (m\n              <jats:sup>6<\/jats:sup>\n              A) modification catalyzed by the METTL3 (methyltransferase-like 3)\u2013containing methyltransferase complex is the most abundant RNA epigenetic modification in eukaryotes, but the role of m\n              <jats:sup>6<\/jats:sup>\n              A RNA methylation in VSMC migration and proliferation and neointima formation remains highly controversial.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS:<\/jats:title>\n            <jats:p>\n              Primary human and rat VSMCs were utilized for in vitro experiments. VSMC-specific METTL3 knockout mice (\n              <jats:italic toggle=\"yes\">Mettl3<\/jats:italic>\n              <jats:sup>flox\/flox<\/jats:sup>\n              <jats:italic toggle=\"yes\">Myh11<\/jats:italic>\n              -CreER\n              <jats:sup>T2<\/jats:sup>\n              ) were generated to explore the role of METTL3 in carotid artery wire injury in vivo. Methylated RNA immunoprecipitation sequencing was performed to screen for genes targeted for METTL3-catalyzed m\n              <jats:sup>6<\/jats:sup>\n              A RNA methylation. Methylation site mapping, methylated RNA immunoprecipitation\u2013quantitative polymerase chain reaction, chromatin immunoprecipitation\u2013quantitative polymerase chain reaction, and reporter gene assays were used to explore how METTL3 modulates target gene expression.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS:<\/jats:title>\n            <jats:p>\n              METTL3 expression was consistently upregulated in the neointima of mice subjected to carotid wire injury and in those of patients who underwent carotid endarterectomy. VSMC-specific METTL3 deficiency significantly attenuated neointima formation in mouse carotid arteries after wire injury. Accordingly, METTL3 ablation markedly repressed VSMC proliferation both in vitro and in vivo. Mechanistically, METTL3 directly catalyzed the m\n              <jats:sup>6<\/jats:sup>\n              A methylation of SGK1 (serum\/glucocorticoid\u2013regulated kinase 1) mRNA and subsequently facilitated its transcription, a process that was dependent on the established association between the SGK1 transcript and SGK1 promoter DNA via recruitment of the m\n              <jats:sup>6<\/jats:sup>\n              A reader YTHDC1 (YT521-B homology domain\u2013containing protein 1). Conversely, SGK1 overexpression abolished the METTL3 deficiency\u2013mediated suppression of VSMC proliferation and postinjury neointima formation.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSIONS:<\/jats:title>\n            <jats:p>\n              METTL3-catalyzed m\n              <jats:sup>6<\/jats:sup>\n              A RNA methylation promoted VSMC proliferation and exacerbated postinjury neointima formation by facilitating YTHDC1-dependent SGK1 gene transcription. Targeting the METTL3-YTHDC1-SGK1 axis to modulate VSMC proliferation may be a potential strategy for in-stent restenosis therapy.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.125.322961","type":"journal-article","created":{"date-parts":[[2025,7,3]],"date-time":"2025-07-03T05:00:22Z","timestamp":1751518822000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":5,"title":["METTL3 Exacerbates Intimal Hyperplasia by Facilitating m\n            <sup>6<\/sup>\n            A-YTHDC1-Dependent SGK1 Gene Transcription"],"prefix":"10.1161","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3778-2398","authenticated-orcid":true,"given":"Jiaqi","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Physiology and Pathophysiology, School of Basic Medical Sciences (J.H., Q.F., Z.D., Z. Li, Y.L., Z. Liu, Q.D., X.Y., F.Y., Y.J., Y.Z., W.K., Y.F.), Peking University, Beijing, China."},{"name":"State Key Laboratory of Vascular Homeostasis and Remodeling (J.H., Q.F., Z.D., Z. Li, Y.L., Z. Liu, Q.D., X.Y., F.Y., Y.J., Y.Z., W.K., Y.F.), Peking University, Beijing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3159-1109","authenticated-orcid":true,"given":"Qianqian","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology, School of Basic Medical Sciences (J.H., Q.F., Z.D., Z. Li, Y.L., Z. Liu, Q.D., X.Y., F.Y., Y.J., Y.Z., W.K., Y.F.), Peking University, Beijing, China."},{"name":"State Key Laboratory of Vascular Homeostasis and Remodeling (J.H., Q.F., Z.D., Z. Li, Y.L., Z. Liu, Q.D., X.Y., F.Y., Y.J., Y.Z., W.K., Y.F.), Peking University, Beijing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3216-8541","authenticated-orcid":true,"given":"Zhigang","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology, School of Basic Medical Sciences (J.H., Q.F., Z.D., Z. Li, Y.L., Z. Liu, Q.D., X.Y., F.Y., Y.J., Y.Z., W.K., Y.F.), Peking University, Beijing, China."},{"name":"State Key Laboratory of Vascular Homeostasis and Remodeling (J.H., Q.F., Z.D., Z. Li, Y.L., Z. Liu, Q.D., X.Y., F.Y., Y.J., Y.Z., W.K., Y.F.), Peking University, Beijing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6655-4687","authenticated-orcid":true,"given":"Zhuofan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology, School of Basic Medical Sciences (J.H., Q.F., Z.D., Z. Li, Y.L., Z. Liu, Q.D., X.Y., F.Y., Y.J., Y.Z., W.K., Y.F.), Peking University, Beijing, China."},{"name":"State Key Laboratory of Vascular Homeostasis and Remodeling (J.H., Q.F., Z.D., Z. Li, Y.L., Z. Liu, Q.D., X.Y., F.Y., Y.J., Y.Z., W.K., Y.F.), Peking University, Beijing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yihan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology, School of Basic Medical Sciences (J.H., Q.F., Z.D., Z. Li, Y.L., Z. Liu, Q.D., X.Y., F.Y., Y.J., Y.Z., W.K., Y.F.), Peking University, Beijing, China."},{"name":"State Key Laboratory of Vascular Homeostasis and Remodeling (J.H., Q.F., Z.D., Z. Li, Y.L., Z. 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