RIPK3 Promotes Acute Pancreatitis via TRAF6-K63 Ubiquitination and Downstream Signaling Activation

RIPK3 Promotes Acute Pancreatitis via TRAF6-K63 Ubiquitination and Downstream Signaling Activation | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article RIPK3 Promotes Acute Pancreatitis via TRAF6-K63 Ubiquitination and Downstream Signaling Activation Shengchuan Chen, Liping Yang, Xiaodong Wang, Xiaosun Liu, Jiren Yu, and 9 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7267490/v1 This work is licensed under a CC BY 4.0 License Status: Under Revision Version 1 posted 9 You are reading this latest preprint version Abstract Acute pancreatitis is a condition characterized by the injury and death of pancreatic acinar cells caused by multiple factors, ultimately leading to local or systemic inflammatory responses. Existing treatment methods for acute pancreatitis, especially severe acute pancreatitis, are still limited. Previous studies have shown that RIPK3 makes a prominent contribution to the regulation of pancreatic acinar cell necroptosis. In this study, our research has found that RIPK3 also plays an indispensable role in regulating the inflammatory response of macrophages. Studies have shown that the RIPK3 inhibitor GSK-872 and conditional knockout of RIPK3 in macrophages effectively alleviate pancreatic tissue damage. It is also elucidated that macrophage RIPK3 interacts with TRAF6, facilitates TRAF6-K63 ubiquitination, triggers the activation of the NF-κB and MPAK inflammatory signaling pathways, rather than through the necroptosis mechanism, and promotes the occurrence and development of acute pancreatitis. This study will focus on exploring the regulatory role and mechanism of RIPK3 in macrophages, providing new strategies and targets for the therapy of acute pancreatitis. Biological sciences/Immunology/Inflammation/Acute inflammation Health sciences/Diseases/Gastrointestinal diseases/Pancreatic disease/Pancreatitis/Acute pancreatitis Acute pancreatitis RIPK3 TRAF6 Macrophage Inflammation Full Text Additional Declarations (Not answered) Supplementary Files SupplementaryRIPK3.docx Supplementary WesternBlotrawdata.pdf Western Blot AbbreviationsRIPK3.docx Abbreviations Cite Share Download PDF Status: Under Revision Version 1 posted Editorial decision: revise 11 Sep, 2025 Review # 1 received at journal 02 Sep, 2025 Review # 2 received at journal 29 Aug, 2025 Reviewer # 2 agreed at journal 19 Aug, 2025 Reviewer # 1 agreed at journal 19 Aug, 2025 Reviewers invited by journal 16 Aug, 2025 Submission checks completed at journal 01 Aug, 2025 Editor assigned by journal 01 Aug, 2025 First submitted to journal 01 Aug, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7267490","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":501250971,"identity":"8c176a49-dc23-4afc-b936-cb5b805ade00","order_by":0,"name":"Shengchuan 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