TY - JOUR
T1 - Protease-activated receptors in kidney disease progression
AU - Palygin, Oleg
AU - Ilatovskaya, Daria V.
AU - Staruschenko, Alexander
N1 - Funding Information:
This manuscript is supported by the National Kidney Foundation Young Investigator Grant (to O. Palygin), National Institutes of Health Grants HL108880, HL122662 (to A. Staruschenko), and DK105160 (to D. Ilatovskaya), Juvenile Diabetes Research Foundation 1-INO-2016-223-A-N (to A. Staruschenko), and the American Diabetes Association Grant 1-15-BS-172 (to A. Staruschenko).
Publisher Copyright:
© 2016 the American Physiological Society.
PY - 2016/12/1
Y1 - 2016/12/1
N2 - Proteaseactivated receptors (PARs) are members of a well-known family of transmembrane G protein-coupled receptors (GPCRs). Four PARs have been identified to date, of which PAR1 and PAR2 are the most abundant receptors, and have been shown to be expressed in the kidney vascular and tubular cells. PAR signaling is mediated by an N-terminus tethered ligand that can be unmasked by serine protease cleavage. The receptors 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 modulates renal hemodynamics and glomerular filtration rate. Clinical studies further demonstrated that the 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 the 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.
AB - Proteaseactivated receptors (PARs) are members of a well-known family of transmembrane G protein-coupled receptors (GPCRs). Four PARs have been identified to date, of which PAR1 and PAR2 are the most abundant receptors, and have been shown to be expressed in the kidney vascular and tubular cells. PAR signaling is mediated by an N-terminus tethered ligand that can be unmasked by serine protease cleavage. The receptors 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 modulates renal hemodynamics and glomerular filtration rate. Clinical studies further demonstrated that the 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 the 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.
KW - Calcium transient
KW - Chronic kidney disease
KW - Perivascular cells
KW - Serine proteases
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U2 - 10.1152/ajprenal.00460.2016
DO - 10.1152/ajprenal.00460.2016
M3 - Review article
C2 - 27733370
AN - SCOPUS:85002958190
SN - 1931-857X
VL - 311
SP - F1140-F1144
JO - American Journal of Physiology - Renal Physiology
JF - American Journal of Physiology - Renal Physiology
IS - 6
ER -