{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T13:56:28Z","timestamp":1787579788667,"version":"build-2736575974"},"reference-count":36,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T00:00:00Z","timestamp":1756339200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Diabetes Invest"],"published-print":{"date-parts":[[2025,11]]},"abstract":"ABSTRACT<\/jats:title>\n \n Introduction<\/jats:title>\n \n Gestational diabetes mellitus (GDM) represents one of the most prevalent medical complications during pregnancy. Emerging evidence has implicated NOL1\/NOP2\/SUN domain (NSUN)2\u2010mediated 5\u2010methylcytosine (m\n 5<\/jats:sup>\n C) methylation modifications in various pathological conditions. This study aimed to investigate the role of m\n 5<\/jats:sup>\n C modification in GDM and to elucidate its underlying mechanisms.\n <\/jats:p>\n <\/jats:sec>\n \n Materials and Methods<\/jats:title>\n \n The mRNA expression levels of m\n 5<\/jats:sup>\n C\u2010related RNA methyltransferases were quantified using reverse transcription\u2010quantitative polymerase chain reaction. Cellular viability and proliferation were assessed through Cell Counting Kit\u20108 and EdU assays. The apoptosis rate was determined by flow cytometry. Western blot was employed to analyze autophagy\u2010related protein expression. The m\n 5<\/jats:sup>\n C modification sites on PTEN\u2010induced putative kinase 1 (PINK1) were identified via dual\u2010luciferase reporter assays. An RNA immunoprecipitation assay was performed to examine NSUN2\u2010PINK1 interactions. Finally, a mouse model was established to further explore the role of NSUN2 in GDM\n in vivo<\/jats:italic>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Our findings revealed elevated NSUN2 expression in HTR\u20108\/SVneo cells. NSUN2\u2010mediated m\n 5<\/jats:sup>\n C modification suppressed proliferation while enhancing apoptosis, inflammation, and autophagy in high glucose (HG)\u2010stimulated HTR\u20108\/SVneo cells. Mechanistically, NSUN2 upregulated PINK1 expression through an m\n 5<\/jats:sup>\n C\u2010dependent regulation. Pharmacological inhibition of PINK1 reversed these effects, enhancing proliferation while attenuating apoptosis, inflammation, and autophagy under HG conditions. Conversely, PINK1 overexpression exacerbated the observed cellular responses.\n In vivo<\/jats:italic>\n , NSUN2 inhibition alleviated inflammation and hyperglycemia in GDM pregnant mice.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n NSUN2\u2010mediated m\n 5<\/jats:sup>\n C modification promoted GDM progression by upregulating PINK1 expression, leading to impaired trophoblast function. Targeting this NSUN2\u2010m\n 5<\/jats:sup>\n C\u2010PINK1 axis may represent a promising therapeutic strategy for GDM management.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/jdi.70140","type":"journal-article","created":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T07:17:07Z","timestamp":1756365427000},"page":"2005-2017","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["NSUN2<\/scp>\n \u2010mediated\n \n m\n 5<\/sup>\n C\n <\/scp>\n methylation modification regulates trophoblast cell proliferation, apoptosis, and autophagy in gestational diabetes mellitus"],"prefix":"10.1111","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-1011-6037","authenticated-orcid":false,"given":"Jiujiu","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Gynaecology and Obstetrics Fengtai District Maternal and Child Health Hospital Beijing City 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