{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:28:34Z","timestamp":1787030914369,"version":"build-2736575974"},"reference-count":50,"publisher":"Korean Diabetes Association","issue":"6","license":[{"start":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T00:00:00Z","timestamp":1747872000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Applied Basic Frontier Special Project of Wuhan Science and Technology Bureau","award":["2020020601012246"],"award-info":[{"award-number":["2020020601012246"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81602858"],"award-info":[{"award-number":["81602858"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["e-dmj.org"],"crossmark-restriction":true},"short-container-title":["Diabetes Metab J"],"published-print":{"date-parts":[[2025,11,1]]},"abstract":"<jats:p>Background: Interleukin 33 (IL33) drives liver fibrosis, and individuals with type 2 diabetes mellitus are more likely advanced to liver fibrosis. However, the role of IL33 in diabetic liver fibrosis remains unclear, prompting our investigation.Methods: We developed a diabetes model in wild-type, IL33&lt;sup&gt;\u2212\/\u2212&lt;\/sup&gt;, and suppression of tumorigenicity 2 (ST2&lt;sup&gt;\u2212\/\u2212&lt;\/sup&gt;, IL33 receptor) mice. Furthermore, wild-type diabetic mice were injected with IL33 neutralizing antibody (\u03b1IL33). We also co-cultured human liver endothelial cells and human hepatic stellate cells to identify the role of IL33 in high palmitic acid and high glucose conditions.Results: Hepatic collagen deposition was increased in diabetic mice, which was alleviated by IL33 knockout, ST2 knockout, or administration of \u03b1IL33. Also, \u03b1IL33 treatment blunted liver sinusoidal endothelial cell (LSEC) dysfunction and inflammation during diabetic liver fibrosis progression. Recombinant IL33 (rIL33) treatment aggravated autophagy disruption in the presence of palm acid and high glucose in LSECs, which was blunted by autophagy agonist rapamycin administration and ERK\/MAPK inhibitor PD98059 treatment. Hepatic stellate cell line LX-2 co-cultured with rIL33-pretreated LSECs displayed augmented activation, which was also attenuated by rapamycin or PD98059 pretreated.Conclusion: IL33 drives LSEC dysfunction and promotes diabetic hepatic fibrosis, thus a potential therapeutic target for diabetic liver fibrosis.<\/jats:p>","DOI":"10.4093\/dmj.2024.0532","type":"journal-article","created":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T01:03:21Z","timestamp":1747875801000},"page":"1204-1218","update-policy":"https:\/\/doi.org\/10.4093\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Interleukin 33 Promotes Liver Sinusoidal Endothelial Cell Dysfunction and Hepatic Fibrosis in Diabetic 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