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Nevertheless, the causal relationship of periodontitis with DN and the underlying molecular mechanisms remain unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>Ligature\u2010induced experimental periodontitis (LIP) was induced in KK\u2010A<jats:sup>y<\/jats:sup> mice to investigate the molecular mechanisms underlying the LIP\u2010mediated aggravation of glomerular pathology in DN. Outpatients with type 2 diabetes (T2D) at Kyushu University Hospital were recruited to confirm the association of renal dysfunction and periodontitis with a urinary factor identified by RNA sequencing (RNA\u2010seq) in the mouse glomeruli.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>LIP aggravated renal dysfunction and glomerular pathologies in KK\u2010A<jats:sup>y<\/jats:sup> mice. RNA\u2010seq in the glomeruli revealed haematopoietic prostaglandin D synthase (HPGDS) as the possible factor bridging periodontitis with DN progression. Glomerular PGD2 levels in KK\u2010Ay mice were significantly elevated by LIP. Oral administration of an HPGDS inhibitor, HQL\u201079, successfully prevented LIP\u2010mediated DN progression in KK\u2010A<jats:sup>y<\/jats:sup> mice by lowering glomerular PGD2 levels. Urinary HPGDS\u2010to\u2010creatinine ratio could be associated with renal dysfunction and periodontitis in outpatients with T2D.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Periodontitis may contribute to DN progression via the glomerular HPGDS\u2013PGD2 axis. These results suggest a novel mechanism in periodontitis\u2010related DN progression.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jcpe.14180","type":"journal-article","created":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T03:34:19Z","timestamp":1750131259000},"page":"1211-1220","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Glomerular Haematopoietic Prostaglandin D Synthase\u2010Prostaglandin <scp>D2<\/scp> Axis Contributes to the Periodontitis\u2010Related Exacerbation of Diabetic Nephropathy in <scp>KK<\/scp>\u2010A<sup>y<\/sup> Mice"],"prefix":"10.1111","volume":"52","author":[{"given":"Kohei","family":"Sato","sequence":"first","affiliation":[{"name":"Section of Periodontology, Faculty of Dental Science Kyushu University  Fukuoka 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