MicroRNA-125a-5p promotes NLRP3/caspase-1/GSDMD pathway-mediated pyroptosis in endothelial cells during Kawasaki disease

Kawasaki disease (KD) is an acute systemic vasculitis that the primary cause of secondary heart disease in children. Dysregulation of microRNA (miRNA) expression drives gene expression patterns across multiple biological processes, thereby mediating the pathogenesis and progression of KD. This study investigated how miR-125a-5p regulates pyroptosis in KD-associated endothelial cells. This study used Lactobacillus casei cell-wall extract (LCWE) to stimulate male C57BL/6 mice and human umbilical vein endothelial cells (HUVECs) to establish KD-like models. Experimental data demonstrated marked upregulation of miR-125a-5p expression in both KD-associated models. In vitro analysis revealed that targeted inhibition of miR-125a-5p increased HUVEC survival while reducing NLRP3/caspase-1/GSDMD-driven pyroptosis. In vivo, targeted inhibition of miR-125a-5p inactivated the NLRP3/caspase-1/GSDMD signaling pathway and diminished pyroptosis and inflammation in coronary artery tissues. This study found that miR-125a-5p exacerbates LCWE-induced pyroptosis in HUVECs and vascular injury in mice, suggesting a potential therapeutic strategy targeting miR-125a-5p for KD-related endothelial injury and inflammation.