Treatment with a PPAR-γ Agonist Protects Against Hyperuricemic Nephropathy in a Rat Model

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Xin Wang,1,* Jin Deng,2,* Chongxiang Xiong,1 Haishan Chen,1 Qin Zhou,1 Yue Xia,1 Xiaofei Shao,1 Hequn Zou1 1Department of Nephrology, The Third Affiliated Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 2Department of Nephrology, The First Affiliated Hospital of University of South China, Hengyang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hequn Zou Tel +86 020-62784391Email zhq1962@smu.edu.cnPurpose: Hyperuricemia is an independent risk factor for renal damage and can promote the progression of chronic kidney disease (CKD). In the present study, we employ a rat model to investigate the effects of rosiglitazone (RGTZ), a peroxisome proliferator-activated receptor-gamma agonist, on the development of hyperuricemic nephropathy (HN), and we elucidate the mechanisms involved.Methods: An HN rat model was established by oral administration of a mixture of adenine and potassium oxonate daily for 3 weeks. Twenty-four rats were divided into 4 groups: sham treatment, sham treatment plus RGTZ, HN, and HN treated with RGTZ.Results: Administration of RGTZ effectively preserved renal function, decreased urine microalbumin, and inhibited interstitial fibrosis and macrophage infiltration in a rat HN model. RGTZ treatment also inhibited TGF-β and NF-κB pathway activation, decreased expression of fibronectin, collagen I, α-SMA, vimentin, MCP-1, RANTES, TNF-α, and IL-1β, and increased E-cadherin expression in the kidneys of HN rats. Furthermore, RGTZ treatment preserved expression of OAT1 and OAT3 in the kidney of HN rats.Conclusion: RGTZ attenuates the progression of HN through inhibiting TGF-β signaling, suppressing epithelial-to-mesenchymal transition, reducing inflammation, and lowering serum uric acid levels by preserving expression of urate transporters.Keywords: hyperuricemic nephropathy, peroxisome proliferator-activated receptor-gamma, rosiglitazone, renal fibrosis, epithelial-to-mesenchymal transition, inflammation

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