title: Differential Roles of Peroxisome Proliferator-Activated Receptor-α and Receptor-γ on Renal Crystal Formation in Hyperoxaluric Rodents.
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.
authors.affiliation: Department of Nephrourology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 4678601, Japan.
authors.forename: Kazumi
authors.initials: K
authors.lastname: Taguchi
authors.affiliation: Department of Nephrourology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 4678601, Japan.
authors.forename: Atsushi
authors.identifier: 0000-0003-2080-3794
authors.initials: A
authors.lastname: Okada
authors.affiliation: Department of Nephrourology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 4678601, Japan.
authors.forename: Shuzo
authors.initials: S
authors.lastname: Hamamoto
authors.affiliation: Department of Nephrourology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 4678601, Japan.
authors.forename: Rei
authors.initials: R
authors.lastname: Unno
authors.affiliation: Department of Nephrourology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 4678601, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Kobayashi
authors.affiliation: Department of Nephrourology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 4678601, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Ando
authors.affiliation: Department of Nephrourology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 4678601, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Tozawa
authors.affiliation: China-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.
authors.forename: Bing
authors.initials: B
authors.lastname: Gao
authors.affiliation: Department of Nephrourology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 4678601, Japan.
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Kohri
authors.affiliation: Department of Nephrourology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 4678601, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Yasui