{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T07:03:40Z","timestamp":1789542220564,"version":"build-2803163510"},"reference-count":52,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T00:00:00Z","timestamp":1778457600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82171681"],"award-info":[{"award-number":["82171681"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81901505"],"award-info":[{"award-number":["81901505"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Chronic low-grade inflammation in gestational diabetes mellitus is one of the significant causes of placental dysfunction. However, the mechanisms by which abnormal glucose metabolism affects inflammation are not fully understood. p66Shc serves as a redox enzyme to regulate reactive oxygen species in mitochondria. Herein, we explore the interaction between p66Shc and OGT. High glucose induces O-GlcNAcylation of p66Shc, which promotes its protein stability and mitochondrial translocation, which induced elevated cytoplasmic mtDNA release and activation of the cGAS\/STING to facilitate cellular senescence and inflammation in trophoblast cells. Specifically, we identify Ser213 may serve as the major site of O-GlcNAcylation on p66Shc. Mutation of Ser213 inhibits the activity of p66Shc, leading to compromised mtDNA release and senescence-associated secretory phenotype levels. We also identified hundreds of genes associated with inflammatory responses and cell cycle transition that are co-regulated by p66Shc and OGT, the deletion of either of which results in diminished level of senescence-associated secretory phenotype. Collectively, our findings highlight the vital role of O-GlcNAcylation in regulating p66Shc and senescence-associated secretory phenotype levels under high glucose, thereby underscoring its potential as a target for therapeutic intervention against gestational diabetes mellitus.<\/jats:p>","DOI":"10.1093\/biolre\/ioag090","type":"journal-article","created":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T11:47:33Z","timestamp":1778240853000},"page":"875-889","source":"Crossref","is-referenced-by-count":0,"title":["O-GlcNAcylation of p66Shc drives senescence-associated secretory phenotype via mitochondrial DNA release in gestational diabetes mellitus"],"prefix":"10.1093","volume":"115","author":[{"given":"Hengxuan","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Histology and Embryology, TaiKang Medical School (School of Basic Medical Sciences), Wuhan University , Wuhan, Hubei Province 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,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiting","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, TaiKang Medical School (School of Basic Medical Sciences), Wuhan University , Wuhan, Hubei Province ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuexiao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, TaiKang Medical School (School of Basic Medical Sciences), Wuhan University , Wuhan, Hubei Province ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanyi","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, TaiKang Medical School (School of Basic Medical Sciences), Wuhan University , Wuhan, Hubei Province 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