{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T13:45:30Z","timestamp":1790948730460,"version":"4.1.0"},"reference-count":59,"publisher":"Wiley","issue":"24","license":[{"start":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T00:00:00Z","timestamp":1755734400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82100679"],"award-info":[{"award-number":["82100679"]}],"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":["82170587"],"award-info":[{"award-number":["82170587"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>Severe acute pancreatitis (SAP) is a critical abdominal condition with high mortality rates. The activation of necroptosis in acinar cells is an critical mechanism for SAP. Pellino1 (PELI1), as an E3 ubiquitin ligase, is involved in pathogenic mechanisms in various diseases. Its ubiquitination function also can regulate necroptosis. However, in SAP, there is a lack of research on upstream regulatory mechanisms and small molecule\u2010targeted drug therapy of necroptosis. Therefore, it is of great significance to study the specific mechanism of PELI1 regulating necroptosis in SAP.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>We designed animals and cells with overexpression and knockdown of PELI1 to study the role of PELI1 in SAP, detect the ubiquitination regulatory mechanism of PELI1 on necroptosis and explore the therapeutic effect of GSK\u2010872 in SAP models in vitro and in vivo.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>We revealed that PELI1 expression was significantly down\u2010regulated in SAP mouse models and in vitro SAP cell models. Additionally, the overexpression experiments at the cellular and animal levels confirmed the protective effect of PELI1 in SAP and its negative regulatory effect on necroptosis. Mechanistically, our investigation identified that PELI1 degraded RIP3 through K48\u2010linked ubiquitination to inhibit necroptosis, and thereby promote acinar cell activity. Furthermore, we found that GSK\u2010872 effectively inhibited necroptosis and alleviated pancreatic damage in SAP.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Implications<\/jats:title>\n                    <jats:p>Our findings highlight the protective role of PELI1\u2010mediated ubiquitination\u2010dependent proteasomal degradation of RIP3 in SAP and propose pharmacological inhibition of RIP3 as a promising strategy to combat SAP.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70175","type":"journal-article","created":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T06:14:47Z","timestamp":1755843287000},"page":"6100-6119","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["E3 ubiquitin ligase Pellino1 suppresses acinar cell necroptosis and alleviates severe acute pancreatitis by promoting ubiquitin\u2010dependent receptor\u2010interacting protein kinase 3 (RIP3) degradation"],"prefix":"10.1111","volume":"182","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-6846-343X","authenticated-orcid":false,"given":"Jiatong","family":"Chen","sequence":"first","affiliation":[{"name":"Department of General Surgery (Hepatopancreatobiliary Surgery) The Affiliated Hospital, Southwest Medical University  Luzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiwei","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of General Surgery (Hepatopancreatobiliary Surgery) The Affiliated Hospital, Southwest Medical University  Luzhou China"},{"name":"Metabolic Hepatobiliary and Pancreatic Diseases Key Laboratory of Luzhou City Academician (Expert) Workstation of Sichuan Province, The Affiliated Hospital, Southwest Medical University  Luzhou 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