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PPAR Research
Volume 2016 (2016), Article ID 9605890, 11 pages
http://dx.doi.org/10.1155/2016/9605890
Research Article

Differential Roles of Peroxisome Proliferator-Activated Receptor-α and Receptor-γ on Renal Crystal Formation in Hyperoxaluric Rodents

1Department of Nephrourology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 4678601, Japan
2China-Japan Kidney Stone Research Center, Key Laboratory of Environment and Population Health of Liaoning Education Ministry, Shenyang Medical College, 146 Huanghe North Street, Shenyang 110034, China

Received 24 November 2015; Accepted 10 February 2016

Academic Editor: Markus P. Kummer

Copyright © 2016 Kazumi Taguchi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Peroxisome proliferator-activated receptors (PPARs) and related inflammatory and oxidative molecule expression were investigated in a hyperoxaluric rodent model to evaluate the in vivo efficacy of PPAR agonists in preventing renal crystal formation. PPAR expression was examined in a mouse hyperoxaluria kidney stone model induced by daily intra-abdominal glyoxylate injection. Therapeutic effects of the PPARα agonist fenofibrate and PPARγ agonist pioglitazone were also assessed in a 1% ethylene glycol-induced rat model of hyperoxaluria. Crystal formation, inflammation, cell injury, apoptosis, and oxidative stress were compared to those of vehicle-treated controls. Quantitative reverse transcription-polymerase chain reaction revealed that PPARα and PPARγ expression decrease and increase, respectively, during crystal formation in hyperoxaluric kidneys. In addition, PPARα localized to the cytoplasm of both proximal and distal tubular cells, whereas PPARγ accumulated in the nucleus of proximal tubular cells. Furthermore, renal crystal formation was significantly less prevalent in pioglitazone-treated rats but higher in the fenofibrate-treated and fenofibrate/pioglitazone-cotreated groups compared to controls, thus indicating that pioglitazone, but not fenofibrate, markedly decreased cell inflammation, oxidative stress, and apoptosis. Collectively, the results demonstrated that PPARγ suppressed renal crystal formation via its antioxidative and anti-inflammatory effects; however, the renotoxicity of PPARα may elicit the opposite effect.