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While metabolic reprogramming, profibrotic extracellular vesicles (EVs), and integrin activation are implicated in pulmonary fibrosis, their interplay remains unclear. This study reveals that succinic acid, a product of glycometabolic reprogramming, promotes macrophage\u2010mediated endocytosis, driving the release of profibrotic EVs. These EVs transfer integrin beta1 (ITG\u03b21) from macrophages to fibroblasts, activating fibroblasts and advancing SAPF. Through Single\u2010cell RNA sequencing (scRNA\u2010seq), proteomics, immunofluorescence, and electron microscopy, the critical role of EV\u2010mediated\u00a0ITG\u03b21 transfer in macrophage\u2010fibroblast communication is identified. Knockdown of ITG\u03b21 or Alix, a mediator of multivesicular bodies (MVBs)\u00a0biogenesis, inhibited profibrotic EVs formation and alleviated SAPF. These findings highlight a novel mechanism in that the transfer ITG\u03b21\u00a0via EVs plays a critical role in macrophage\u2010fibroblast communication, representing a novel mechanism underlying SAPF. Targeting EV\u2010mediated ITG\u03b21 transfer can provide a promising therapeutic strategy to alleviate the progression of SAPF.<\/jats:p>","DOI":"10.1002\/advs.202507411","type":"journal-article","created":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T03:21:45Z","timestamp":1756869705000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Succinic Acid\u2010Induced Macrophage Endocytosis Promotes Extracellular Vesicle\u2010Based Integrin Beta1 Transfer Accelerating Fibroblast Activation and Sepsis\u2010Associated Pulmonary Fibrosis"],"prefix":"10.1002","volume":"12","author":[{"given":"Wenyu","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Critical Care Medicine Renji Hospital Shanghai Jiao Tong University School of Medicine  Shanghai 200127 China"},{"name":"Key Laboratory of Anesthesiology (Shanghai Jiao Tong University) Ministry of Education  Shanghai 200127 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