{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T12:01:02Z","timestamp":1784894462520,"version":"3.55.0"},"reference-count":40,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T00:00:00Z","timestamp":1784851200000},"content-version":"vor","delay-in-days":204,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"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":["Journal of Diabetes Research"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>Worldwide, diabetic retinopathy (DR) stands as a leading cause of vision loss. However, the involvement of PANoptosis\u2014a form of inflammatory cell death that combines features of apoptosis, pyroptosis, and necroptosis\u2014in the development of DR has not been fully elucidated. This study investigated the molecular mechanisms underlying high glucose (HG)\u2013induced PANoptosis in human retinal microvascular endothelial cells (hRMECs), focusing on the scavenger receptor CD36 and NOTCH\/MAML signaling. HG specifically induced PANoptosis in hRMECs, evidenced by concurrent activation of apoptotic, pyroptotic, and necroptotic markers, along with PANoptosome complex formation and morphological validation via terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. HG significantly upregulated CD36 expression and activated the NOTCH\/MAML pathway. CD36 overexpression exacerbated PANoptosis by enhancing cell death, inflammatory responses, and oxidative stress, whereas CD36 knockdown conferred protection. Mechanistically, CD36 promoted PANoptosome assembly through NOTCH\/MAML pathway activation, as demonstrated by increased NICD\u2010MAML1 nuclear colocalization and enhanced NOTCH component expression. We further verified that the CD36\u2010NOTCH axis regulates PANoptosis through the modulation of NLRP3, a core component of the PANoptosome. Pharmacological NOTCH inhibition using DAPT ameliorated HG\u2010induced PANoptosis, whereas NOTCH activation mimicked CD36 overexpression effects. These results establish a novel CD36\u2010NOTCH\/MAML\u2010NLRP3\u2010PANoptosis regulatory pathway in diabetic retinal endothelial cells. This discovery provides crucial insights into DR pathogenesis and pinpoints potential targets for therapeutic intervention.<\/jats:p>","DOI":"10.1155\/jdr\/9324498","type":"journal-article","created":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T11:03:38Z","timestamp":1784891018000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["CD36 Regulates PANoptosis in Diabetic Retinopathy via the NOTCH\/MAML 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