PPAR γ in kidney physiology and pathophysiology

Abstract

Involvement of the nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR γ) in kidney physiology has been explored recently. Synthetic PPAR γ ligands can ameliorate the diabetic kidney disease through different mechanisms, involving inhibition of mesangial cell growth, reduction of mesangial matrix, and cytokine production of glomerular cells as well as promoting endothelial cell survival within the kidney glomeruli. Activation of PPAR γ has additional profibrotic consequences, which can contribute to wound healing in diabetic glomerulonephritis. Beside many beneficial effects, PPAR γ activation, however, can lead to severe water retention, a common side effect of thiazolidinedione therapy. This unwanted effect is due to the activation of PPAR γ in the mesonephric distal collecting system, where PPAR γ positively regulates sodium and water resorbtion leading to the expansion of interstitial fluid volume. Recent studies indicate that PPAR γ is also involved in the normal kidney development, renal lipid metabolism, and activation of the renin-angiotensin system. In this paper, we give a synopsis of the current knowledge on PPAR γ functions in kidney phyisology and pathophysiology.