Fig. 7

Schematic of the mechanism by which CXCR2 bridge the vicious circle between inflammation and glycocalyx degradation by NF-κB p65 signaling pathway. Graphical representation depicting how endothelial CXCR2 deficiency attenuates renal inflammation and glycocalyx shedding through NF-κB signaling in diabetic kidney disease. GEnC and endothelial glycocalyx, GBM and podocytes form the glomerular filtration barrier. CXCL1 and CXCL8, as ligands of CXCR2, bind to CXCR2 and initiate the NF-κB p65 signaling pathway. In DKD, this activation leads to the release of inflammatory factors, endothelial cell activation, and recruitment of macrophages and neutrophils to the endothelial cell surface. These recruited cells further release inflammatory factors and chemokines, ultimately resulting in glycocalyx shedding. Shedding of the endothelial glycocalyx triggers glomerular inflammation and may also initiate crosstalk between endothelial cells and podocytes, leading podocyte injury (podocyte foot processes loss) and leading to proteinuria. Endothelial CXCR2 knockout significantly improves this process