Endothelial Piezo1 stimulates angiogenesis to offer protection against intestinal ischemia–reperfusion injury in mice

作者：Cuifen Wang, Shangfei Luo, Yameng Yan, Jinze Li, Jinze Li, Weipin Niu, Tianying Hong, Kai Hao, Xin Sun, Jiali Liu, Ran An, Jing Li, Jing Li · 发表于：Molecular Medicine · 年份：2025 · DOI：10.1186/s10020-025-01197-3 · 被引用次数：8 · 研究领域：Erythrocyte Function and Pathophysiology、Blood properties and coagulation、Phagocytosis and Immune Regulation

Abstract Background Intestinal ischemia–reperfusion (I/R) injury, which occurs in the ileum and not only leads to intestinal tissue damage, but also may trigger systemic inflammatory responses, is a prevalent pathological condition that is typically associated with acute intestinal ischemia, surgical procedures, or trauma. However, the precise underlying pathogenic mechanisms have not yet been fully uncovered. In this study, we explored the specific roles and underlying mechanisms by which endothelial Piezo1 is involved in intestinal I/R injury. Methods We evaluated the roles of Piezo1 using both in vivo mouse intestinal ischemia–reperfusion (I/R) injury and in vitro hypoxia-reoxygenation (H/R) models. The expression of Piezo1 was assessed using immunofluorescence and RT-qPCR. In vivo and in vitro experiments involving endothelial knockout and activation of Piezo1 with the specific agonist Yoda1 were conducted to observe the effects on angiogenesis and injury. Results We found that in post-intestinal I/R mice, Piezo1 expression was markedly increased and was mainly abundant in ileum endothelial cells. Specific knockout of endothelial Piezo1 exhibited a more severe phenotype characterized by accelerating damage to the ileum structure, increasing inflammatory response, and inhibiting angiogenesis. Yoda1-mediated activation of Piezo1 significantly ameliorated intestinal I/R injury. Activation of Piezo1 induced by Yoda1 or H/R promoted angiogenesis in Human Umbilical Vein Endothe...