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(Pro)renin receptor contributes to diabetic nephropathy by enhancing renal inflammation

Luis C Matavelli1, Jiqian Huang, Helmy M Siragy

  • 1Department of Medicine, University of Virginia Health System, Charlottesville, VA, USA.

Clinical and Experimental Pharmacology & Physiology
|September 23, 2009
PubMed

Insights

The (pro)renin receptor (PRR) contributes to diabetic kidney disease by increasing inflammatory cytokines, independent of angiotensin II. Blocking the PRR reduces kidney damage and inflammation in diabetic rats.

Area of Science:

  • Nephrology
  • Endocrinology
  • Immunology

Background:

  • The (pro)renin receptor (PRR) mediates effects of renin and prorenin, influencing blood pressure and kidney function.
  • PRR expression is elevated in diabetic kidneys, but its specific role in diabetic nephropathy remains unclear.
  • Diabetic nephropathy is characterized by kidney damage and inflammation, involving cytokines like TNF-alpha and IL-1beta.

Purpose of the Study:

  • To investigate the contribution of the PRR to diabetic nephropathy.
  • To examine the role of PRR in enhancing renal production of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta).

Main Methods:

  • Streptozotocin-induced diabetic Sprague-Dawley rats were treated with a PRR blocker (PRRB), valsartan (AT1 receptor antagonist), or combination therapy via osmotic minipumps.
  • Evaluated urine albumin:creatinine ratio (UACR), renal interstitial fluid (RIF) levels of Angiotensin II (AngII), TNF-alpha, and IL-1beta.
  • Assessed renal expression of TNF-alpha and IL-1beta, and PRR expression.

Main Results:

  • Diabetic rats showed increased UACR and RIF levels of AngII, TNF-alpha, and IL-1beta compared to controls.
  • PRRB or valsartan treatment, alone or combined, significantly reduced UACR and RIF levels of TNF-alpha and IL-1beta.
  • Renal TNF-alpha and IL-1beta expression decreased with PRRB or valsartan treatment.
  • PRR expression increased in untreated and PRRB-treated diabetic rats, while valsartan reduced it.
  • PRRB did not affect RIF AngII, but valsartan increased it.

Conclusions:

  • The PRR contributes to diabetic kidney disease progression by promoting renal production of inflammatory cytokines TNF-alpha and IL-1beta.
  • These PRR-mediated inflammatory effects occur independently of renal Angiotensin II.
  • Targeting the PRR may offer a therapeutic strategy for diabetic nephropathy.

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