Protease-activated receptors in kidney disease progression

Oleg Palygin, Daria V. Ilatovskaya, Alexander Staruschenko

Research output: Contribution to journalReview articlepeer-review

26 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)F1140-F1144
JournalAmerican Journal of Physiology - Renal Physiology
Volume311
Issue number6
DOIs
StatePublished - Dec 1 2016
Externally publishedYes

Keywords

  • Calcium transient
  • Chronic kidney disease
  • Perivascular cells
  • Serine proteases

ASJC Scopus subject areas

  • Physiology
  • Urology

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