Induction of PPAR Gamma mRNA and Protein Expression by Rosiglitazone in Chronic Cyclosporine Nephropathy in the Rat

ABSTRACT

PURPOSE: We recently reported that rosiglitazone (RGTZ), a peroxisome proliferator-activated receptor gamma (PPARgamma) agonist, has a protective effect against cyclosporine (CsA)- induced renal injury. Here we report the effect of RGTZ on peroxisome proliferator-activated receptor gamma (PPARgamma) expression in an experimental model of chronic cyclosporine (CsA) nephropathy. MATERIALS AND METHODS: Chronic CsA nephropathy was induced in Sprague-Dawley rats by administering CsA (15mg/kg per day) for 28 days, and control rats were treated with vehicle (VH group, olive oil 1mL/kg per day) for 28 days. RGTZ (3mg/kg) was concurrently administered via gavage to the CsA and VH groups. Expression of PPARgamma mRNA and protein was evaluated with RT-PCR, immunohistochemistry, and immunoblotting. RESULTS: PPARgamma mRNA expression was similar to the level of PPARgamma protein constitutively expressed in the kidneys of the VH treated rats, with expression in the glomerular epithelial, distal tubular cells, and collecting tubular cells. PPARgamma protein expression in CsA-treated rat kidneys was significantly less than in the VH group. However, concomitant administration of RGTZ restored PPARgamma protein expression in the kidneys of the CsA- reated rats. CONCLUSION: Exogenous administration of RGTZ treatment upregulates PPARgamma expression and that this mechanism may play a role in protecting against CsA-induced renal injury.