{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:56:47Z","timestamp":1790125007942,"version":"4.0.1"},"reference-count":37,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,9,25]],"date-time":"2024-09-25T00:00:00Z","timestamp":1727222400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2024,9,25]],"date-time":"2024-09-25T00:00:00Z","timestamp":1727222400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Periodontal Research"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>The high glucose (HG) environment in diabetic periodontitis aggravates the damage of periodontal tissue. Pyroptosis has been shown to be positively correlated with the severity of periodontitis, including macrophage pyroptosis. O\u2010GlcNAcylation is a posttranslational modification that is involved in the pathogenesis of periodontitis. However, whether HG regulates macrophage pyroptosis through O\u2010GlcNAcylation remains uncertain. This study aimed to investigate the effect of HG on the O\u2010GlcNAcylation level of a pyroptosis regulator GSDME in macrophages to further probe the mechanisms of diabetic periodontitis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Blood samples were collected from patients with diabetic periodontitis. THP\u20101 monocytes were induced to differentiate into macrophages by phorbol 12\u2010myristate 13\u2010acetate and then treated with HG to simulate periodontitis in\u00a0vitro. GSDME expression of blood samples and macrophages was measured by quantitative real\u2010time PCR. Pyroptosis was assessed by propidium iodide staining, measurement of cell viability, cytotoxicity, protein levels of inflammation factors, and pyroptosis\u2010related proteins. O\u2010GlcNAcylation of GSDME was analyzed using co\u2010immunoprecipitation (co\u2010IP), IP, and western blot.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The results showed that GSDME expression was elevated in patients with periodontitis and HG\u2010treated macrophages. HG inhibited cell viability but increased LDH content, levels of IL\u20101\u03b2, IL\u201018, TNF\u2010\u03b1, NLRP3, GSDMD, and Caspase\u20101, indicating that HG promoted pyroptosis of macrophages, which was reversed by GSDME knockdown. HG treatment increased O\u2010GlcNAcylation in macrophages. Mechanically, GSDME interacted with OGT, and OGT knockdown suppressed O\u2010GlcNAcylation of GSDME at Ser (S)339 site. Knockdown of OGT inhibited pyroptosis in HG\u2010treated macrophages, while GSDME overexpression partially reversed this inhibition.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>HG treatment enhanced OGT\u2010mediated GSDME O\u2010GlcNAcylation, thereby augmenting pyroptosis in LPS\u2010induced macrophages. These results may provide a novel sight for the treatment of periodontitis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jre.13349","type":"journal-article","created":{"date-parts":[[2024,9,25]],"date-time":"2024-09-25T06:09:19Z","timestamp":1727244559000},"page":"581-589","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["High glucose promotes lipopolysaccharide\u2010induced macrophage pyroptosis through GSDME O\u2010GlcNAcylation"],"prefix":"10.1111","volume":"60","author":[{"given":"Huifeng","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Stomatology Inner Mongolia Autonomous Region People's Hospital  Hohhot City Inner Mongolia 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