The Effect of PPARy Ligands in Nondiabetic Renal Disease

In nondiabetic models of glomerulosclerosis, PPAR-y ligands are also effective in preventing renal dysfunction. In the 5/6 nephrectomized rat, treatment with troglitazone significantly reduced proteinuria, serum creatinine level, and glomerulosclerosis through the inhibition of glomerular cell proliferation and reduction of glomerular and tubular TGF-0 expression (138). In cultured mouse MCs, pioglitazone inhibits TGF-0-induced fibronectin expression by inhibiting the PPAR-y dependent activation of AP-1, whereas 15dPGJ2 also inhibits TGF-0-induced fibronectin expression through a dual mechanism that is both dependent on and independent of PPAR-y activation (Fig. 3C) (139).

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