Induction of PPAR Gamma mRNA and Protein Expression by Rosiglitazone in Chronic Cyclosporine Nephropathy in the Rat
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Abstract
Purpose: We recently reported that rosiglitazone (RGTZ), a peroxisome proliferator-activated receptor gamma (PPARγ) agonist, has a protective effect against cyclosporine (CsA)- induced renal injury. Here we report the effect of RGTZ on peroxisome proliferator-activated receptor gamma (PPARγ) 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 PPARγ mRNA and protein was evaluated with RT-PCR, immunohistochemistry, and immunoblotting. Results: PPARγ mRNA expression was similar to the level of PPARγ protein constitutively expressed in the kidneys of the VH treated rats, with expression in the glomerular epithelial, distal tubular cells, and collecting tubular cells. PPARγ protein expression in CsA-treated rat kidneys was significantly less than in the VH group. However, concomitant administration of RGTZ restored PPARγ protein expression in the kidneys of the CsA- reated rats. Conclusion: Exogenous administration of RGTZ treatment upregulates PPARγ expression and that this mechanism may play a role in protecting against CsA-induced renal injury.
참고문헌 (23)
- Bennett WM, "Chronic cyclosporine nephropathy: the Achilles' heel of immunosuppressive therapy", 50, pp.1089~1100 (1996)
- Campistol JM, "Mechanisms of nephrotoxicity", 69, pp.S5~S10 (2000)
- Pichler RH, "Pathogenesis of cyclosporine nephropathy: roles of angiotensin II and osteopontin", 6, pp.1186~1196 (1995)
- Guan Y, "Peroxisome proliferator-activated receptors (PPARs): novel therapeutic targets in renal disease", 60, pp.14~30 (2001)
- Sato K, "Expression of peroxisome proliferator-activated receptor isoform proteins in the rat kidney", 27, pp.417~425 (2004)
- Buckingham RE, "Peroxisome proliferator-activated receptor-gamma agonist, rosiglitazone, protects against nephropathy and pancreatic islet abnormalities in Zucker fatty rats", 47, pp.1326~1334 (1998)
- "In vivo myocardial protection from ischemia", reperfusion injury by the peroxisome proliferator- activated receptor-gamma agonist rosiglitazone, 2001, pp.104, 2588~2594
- "Ligands of the peroxisome proliferator-activated receptors (PPAR-gamma and PPAR-alpha) reduce myocardial infarct size", 161, pp.1027~1040 (2002)
- "Rosiglitazone protects against cyclosporine- induced pancreatic and renal injury in rats", 5, pp.1856~1867 (2005)
- "Isoform-specific retinoid-X receptor (RXR) antibodies detect differential expression of RXR proteins in the pituitary gland", 136, pp.1766~1774 (1995)
- "Long-term treatment with cyclosporine decreases aquaporins and urea transporters in the rat kidney.", 287, pp.F139~F151 (2004)
- "Synergistic effects of mycophenolate mofetil and losartan in a model of chronic cyclosporine nephropathy", 75, pp.309~315 (2003)
- "Expression of peroxisomal proliferator- activated receptors and retinoid X receptors in the kidney", 277, pp.F966~F973 (1999)
- "Apoptosis and necrosis: mechanisms of cell death induced by cyclosporine A in a renal proximal tubular cell line", 54, pp.1955~1966 (1998)
- "Cyclosporine nephrotoxicity: the mechanisms of cell injury by cyclosporine A in renal proximal tubular cells", 32, pp.1621~1622 (2000)
- "Potentiation by nitric oxide of cyclosporin A and FK506-induced apoptosis in renal proximal tubule cells", 11, pp.2315~2323 (2000)
- "Cyclosporine A-induced renal fibrosis: a role for epithelial-mesenchymal transition", 167, pp.395~407 (2006)
- "Cyclosporine A induced epithelial- mesenchymal transition in human renal proximal tubular epithelial cells", 20, pp.2215~2225 (2005)
- "Calcineurin inhibitors and proximal renal tubular injury in renal transplant patients with proteinuria and chronic allograft nephropathy", 79, pp.119~122 (2005)
- "Influence of the renin-angiotensin system on epidermal growth factor expression in normal and cyclosporine-treated rat kidney", pp.847~857
- "Transcription suppression of thromboxane receptor gene by peroxisome proliferator- activated receptor-gamma via an interaction with Sp1 in vascular smooth muscle cells", 277, pp.9676~9683 (2002)
- "Effect of nifedipine in cyclosporine-induced nephrotoxicity in rats: roles of the thromboxane and endothelin systems", 63, pp.263~269 (2000)
- "Role of prostanoids and endothelins in the prevention of cyclosporine-induced nephrotoxicity", 64, pp.231~239 (2001)