Protease-activated receptors (PARs) are a well-known family of transmembrane G-protein-coupled receptors (GPCRs). To date, four PARs have been identified and PAR1 and PAR2 are the most abundant receptors, which were shown to be expressed in the kidney vascular and tubular cells. PAR signaling is mediated by an N-terminus tethered ligands that can be unmasked by serine protease cleavage. PARs are activated by endogenous serine proteases, such as thrombin (acts on PARs 1, 3 and 4) and trypsin (PAR2). PARs can be involved in glomerular, microvascular and inflammatory regulation of renal function in both normal and pathological conditions. As an example, it was shown that human glomerular epithelial and mesangial cells express PARs, and these receptors are involved in the pathogenesis of crescentic glomerulonephritis, glomerular fibrin deposition and macrophage infiltration. Activation of these receptors in the kidney also directly modulates renal hemodynamics and glomerular filtration rate. Clinical studies further demonstrated that concentration of urinary thrombin is associated with glomerulonephritis and type 2 diabetic nephropathy; thus molecular and functional mechanisms of PARs activation can be directly involved in renal disease progression. We briefly discuss here some recent literature related to activation of PAR signaling in glomeruli and the kidney in general and provide some examples of PAR1 signaling in glomeruli podocytes.
- serine proteases
- perivascular cells
- calcium transient
- chronic kidney disease
- Copyright © 2016, American Journal of Physiology-Renal Physiology