Serine proteases and protease-activated receptors signaling in the kidney

Protease-activated receptors (PARs) are a subclass of G protein-coupled receptors activated by serine proteases via proteolytic cleavage, triggering intracellular signaling cascades that regulate various physiological processes. Recent research underscores the significance of serine proteases and PARs in renal physiology, particularly in glomerular cells, where they modulate podocyte function, mesangial matrix dynamics, and filtration barrier integrity. In this review, we discuss the current knowledge on the function of key serine proteases in the kidney and their interactions with specific PARs, with a focus on the glomerulus and pathological implications. Among PARs, PAR1 is the most abundantly expressed in the kidney and plays a pivotal role in renal pathology. Serine proteases such as thrombin, plasmin, and kallikrein interact with PARs to regulate renal function; however, dysregulation in this pathway may contribute to diabetic nephropathy, glomerulosclerosis, fibrosis, and chronic kidney disease. Overall, the role of PARs in glomerular pathophysiology represents a critical area of research with significant therapeutic implications. Continued investigation into the mechanisms of serine proteases and PARs is essential for advancing targeted therapies for glomerular disorders.