KMID : 0311120070480020308
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Yonsei Medical Journal 2007 Volume.48 No. 2 p.308 ~ p.316
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Induction of PPAR Gamma mRNA and Protein Expression by Rosiglitazone in Chronic Cyclosporine Nephropathy in the Rat
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Ahn Kyung-Ohk
Lim Sun-Woo Yang Hyun-Joo Li Can Sugawara Akira Ito Sadayoshi Choi Bum-Soon Kim Yong-Soo Kim Jin Yang Chul-Woo
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Abstract
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Purpose: We recently reported that rosiglitazone (RGTZ), a peroxisome proliferator-activated receptor gamma (PPAR¥ã) agonist, has a protective effect against cyclosporine (CsA)- induced renal injury. Here we report the effect of RGTZ on peroxisome proliferator-activated receptor gamma (PPAR¥ã) expression in an experimental model of chronic cyclosporine (CsA) nephropathy.
Materials & 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 PPAR¥ã mRNA and protein was evaluated with RT-PCR, immunohistochemistry, and immunoblotting.
Results: PPAR¥ã mRNA expression was similar to the level of PPAR¥ã protein constitutively expressed in the kidneys of the VH treated rats, with expression in the glomerular epithelial, distal tubular cells, and collecting tubular cells. PPAR¥ã protein expression in CsA-treated rat kidneys was significantly less than in the VH group. However, concomitant administration of RGTZ restored PPAR¥ã protein expression in the kidneys of the CsA- reated rats.
Conclusion: Exogenous administration of RGTZ treatment upregulates PPAR¥ã expression and that this mechanism may play a role in protecting against CsA-induced renal injury.
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KEYWORD
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Cyclosporin, rosiglitazone, PPAR gamma, nephrotoxicity
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