Young Investigator's Award Finals

Objectives: In IBD patients, elevated mesenteric blood flow alters mechanical forces in intestinal vascular endothelial cells (VECs).These cells sense changes via the mechanosensitive ion channel Piezo1, converting mechanical stimuli into inflammatory signals and inducing inflammation.VECs also secrete lactate, contributing to inflammation.The role of Piezo1 in regulating intestinal vascular lactate metabolism in IBD remains unclear.Materials and Methods: Single-cell sequencing was performed on colon tissues from IBD patients and healthy controls to investigate Piezo1 expression and lactate metabolism.Endothelial cell-specific Piezo1 knockout (Piezo1iEC/iEC) mice were generated and subjected to DSS-induced colitis.Inflammation severity, lactate levels in endothelial cells and plasma, and macrophage polarization were measured.HIF-1-MCT signaling was explored.Results: Piezo1 expression was significantly higher in the colonic mucosa of active IBD patients and DSS-induced colitis mice compared to controls.Single-cell sequencing showed Piezo1 enrichment in intestinal VECs in active IBD.Piezo1iEC/iEC mice with DSS-induced colitis showed reduced IL-6, TNF-, IL-1 levels, decreased M1 macrophage activation, and lower lactate levels compared to controls.Piezo1 knockdown inhibited HIF-1 and MCT expression in VECs.Conclusion: Mechanical force activates Piezo1 in VECs, regulating lactate metabolism via the HIF-1-MCT axis and promoting M1 macrophage differentiation, thereby mediating intestinal inflammation in IBD.This study offers new therapeutic targets for IBD management.