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The role of annexin A3 (ANXA3) in regulating endothelial permeability and inflammation during sepsis is explored using ANXA3 knockout mice and primary human umbilical vein endothelial cells (HUVECs). The absence of ANXA3 exacerbated sepsis outcomes, including increased mortality, lung injury, leukocyte infiltration, and vascular permeability. ANXA3 is highly expressed in endothelial cells and its loss results in the formation of cytoskeletal stress fibers and a decrease in the expression of the junction proteins zonula occludens (Zo)\u20101, vascular endothelial (VE)\u2010cadherin, and claudin 5, leading to increase permeability. ANXA3 knockdown also upregulates E\u2010selectin (CD62E) expression through the phosphorylation of activating transcription factor 2 (ATF2), which increases monocyte adhesion in HUVECs after LPS stimulation. Inhibiting actin polymerization reverse these effects. Thus, ANXA3 stabilizes the actin cytoskeleton, playing a protective role in endothelial dysfunction during sepsis.<\/jats:p>","DOI":"10.1002\/advs.202416904","type":"journal-article","created":{"date-parts":[[2025,3,30]],"date-time":"2025-03-30T15:25:27Z","timestamp":1743348327000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Annexin A3 Represses Endothelial Permeability and Inflammation During Sepsis via Actin Cytoskeleton Modulation"],"prefix":"10.1002","volume":"12","author":[{"given":"Manyu","family":"Xing","sequence":"first","affiliation":[{"name":"Department of Anesthesiology Xiangya Hospital Central South University  Changsha 410008 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Xiangya Hospital Central South University  Changsha 410008 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