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However, the underlying mechanisms and potential therapeutic targets remain unclear. Previous results suggest Src may be involved in regulating the NETs formation. Here, Src is found activated in the NETs model in vitro, in the murine\u2010 and human\u2010derived neutrophils (acute pancreatitis and sepsis). Moreover, p\u2010Src expression correlates with the clinical prognosis of acute pancreatitis and sepsis patients. Meanwhile, the inhibition of Src activity (gene silencing or inhibitors) inhibits NETs formation in vitro. Mechanistically, Src directly activates RAF1 by regulating phosphorylation at the Ser 621 site and mediates the RAF\/MEK\/ERK pathway, thereby affecting the intracellular ROS production. Alternatively, Src activates the RAF\/MEK\/ERK pathway by mediating PKC phosphorylation. In vivo, neutrophil Src \u2010 specific defect significantly reduces acute inflammatory response, organ damage, and the NETs formation in damaged tissue. Eventually, Src inhibitors are used and validated their pharmacological effects. These results identify Src as a key mediator in intracellular ROS production, NETs formation, and acute organ injury. Hence, Src inhibition may represent a promising therapeutic strategy for treating acute organ injury.<\/jats:p>","DOI":"10.1002\/advs.202506028","type":"journal-article","created":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T03:49:02Z","timestamp":1756266542000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Src Reduces Neutrophil Extracellular Traps Generation and Resolves Acute Organ Damage"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8325-0405","authenticated-orcid":false,"given":"Guotao","family":"Lu","sequence":"first","affiliation":[{"name":"Pancreatic Center, Department of Gastroenterology The Affiliated Hospital of Yangzhou University Yangzhou University Yangzhou Jiangsu 225000 China"},{"name":"Yangzhou Key Laboratory of Pancreatic Disease The Affiliated Hospital of Yangzhou University Yangzhou University Yangzhou Jiangsu 225000 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