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Current therapies are mostly supportive, highlighting the critical need for targeted interventions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Transglutaminase 2 (TGM2) was identified via public transcriptomic analysis. Its function was validated in caerulein\u2010induced AP mice and in vitro cell models; mechanisms were explored via Co\u2010IP, ChIP, and dual\u2010luciferase assays. A lactoferrin\u2010modified, ROS\u2010responsive LF\u2010LNP system was developed for TGM2 siRNA delivery.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>TGM2 was upregulated in AP; its inhibition alleviated pancreatic injury and inflammation. Mechanistically, TGM2 bound STAT6 to suppress its phosphorylation\/nuclear translocation, downregulating efferocytosis\u2010related GAS6 and impairing macrophage efferocytosis. LF\u2010LNP@si\u2010TGM2 targeted pancreatic macrophages, silenced TGM2, restored the STAT6\u2013GAS6 axis, enhanced efferocytosis, and reduced inflammation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study identifies TGM2 as a key regulator of AP macrophage efferocytosis via the novel TGM2\u2013STAT6\u2013GAS6 axis. LF\u2010LNP@si\u2010TGM2 is a promising targeted strategy for AP, potentially shifting treatment from supportive to precision therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/advs.202520739","type":"journal-article","created":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T06:51:21Z","timestamp":1771397481000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["TGM2 Aggravates Acute Pancreatitis by Impairing Macrophage Efferocytosis Through Inhibition of the STAT6\u2013GAS6 Axis"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5408-4746","authenticated-orcid":false,"given":"Xuxu","family":"Liu","sequence":"first","affiliation":[{"name":"Key Laboratory of Hepatosplenic Surgery Ministry of Education The First Affiliated Hospital of Harbin Medical University  Harbin 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