Adenosine A2A receptor activation prevents progressive kidney fibrosis in a model of immune-associated chronic inflammation Academic Article uri icon

Overview

MeSH Major

  • Adenosine
  • Adenosine A2 Receptor Agonists
  • Anti-Inflammatory Agents
  • Glomerulonephritis
  • Kidney
  • Phenethylamines
  • Receptor, Adenosine A2A

abstract

  • Crescentic glomerulonephritis (GN) in Wistar-Kyoto rats progresses to lethal kidney failure by macrophage (Mφ)-mediated mechanisms. Mφs in nephritic glomeruli express adenosine A2A receptors (A2ARs), the activation of which suppresses inflammation. Here, we pharmacologically activated the A2ARs with a selective agonist, CGS 21680, and inactivated them with a selective antagonist, ZM241385, to test the effects on established GN. When activation was delayed until antiglomerular basement membrane GN and extracellular matrix deposition were established, glomerular Mφ infiltration was reduced by 83%. There was also a marked improvement in glomerular lesion histology, as well as decreased proteinuria. A2AR activation significantly reduced type I, III, and IV collagen deposition, and E-cadherin expression was restored in association with a reduction of α-smooth muscle actin-positive myofibroblasts in the interstitium and glomeruli. In contrast, pharmacological inactivation of A2ARs increased glomerular crescent formation, type I, III, and IV collagen expression, and enhanced E-cadherin loss. Activation of A2ARs suppressed the expression of the Mφ-linked glomerular damage mediators, transforming growth factor-β, osteopontin-1, thrombospondin-1, and tissue inhibitor of metalloproteinase-1. Thus, A2AR activation can arrest GN and prevent progressive fibrosis in established pathological lesions.Kidney International advance online publication, 20 April 2011; doi:10.1038/ki.2011.101.

publication date

  • April 20, 2011

Research

keywords

  • Academic Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1038/ki.2011.101

PubMed ID

  • 21508927

Additional Document Info