Cargando…
Differential Roles of Peroxisome Proliferator-Activated Receptor-α and Receptor-γ on Renal Crystal Formation in Hyperoxaluric Rodents
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 hyperoxalu...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi Publishing Corporation
2016
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4789040/ https://www.ncbi.nlm.nih.gov/pubmed/27022389 http://dx.doi.org/10.1155/2016/9605890 |
_version_ | 1782420807635435520 |
---|---|
author | Taguchi, Kazumi Okada, Atsushi Hamamoto, Shuzo Unno, Rei Kobayashi, Takahiro Ando, Ryosuke Tozawa, Keiichi Gao, Bing Kohri, Kenjiro Yasui, Takahiro |
author_facet | Taguchi, Kazumi Okada, Atsushi Hamamoto, Shuzo Unno, Rei Kobayashi, Takahiro Ando, Ryosuke Tozawa, Keiichi Gao, Bing Kohri, Kenjiro Yasui, Takahiro |
author_sort | Taguchi, Kazumi |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4789040 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-47890402016-03-28 Differential Roles of Peroxisome Proliferator-Activated Receptor-α and Receptor-γ on Renal Crystal Formation in Hyperoxaluric Rodents Taguchi, Kazumi Okada, Atsushi Hamamoto, Shuzo Unno, Rei Kobayashi, Takahiro Ando, Ryosuke Tozawa, Keiichi Gao, Bing Kohri, Kenjiro Yasui, Takahiro PPAR Res Research Article 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. Hindawi Publishing Corporation 2016 2016-02-28 /pmc/articles/PMC4789040/ /pubmed/27022389 http://dx.doi.org/10.1155/2016/9605890 Text en Copyright © 2016 Kazumi Taguchi et al. https://creativecommons.org/licenses/by/4.0/ 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. |
spellingShingle | Research Article Taguchi, Kazumi Okada, Atsushi Hamamoto, Shuzo Unno, Rei Kobayashi, Takahiro Ando, Ryosuke Tozawa, Keiichi Gao, Bing Kohri, Kenjiro Yasui, Takahiro Differential Roles of Peroxisome Proliferator-Activated Receptor-α and Receptor-γ on Renal Crystal Formation in Hyperoxaluric Rodents |
title | Differential Roles of Peroxisome Proliferator-Activated Receptor-α and Receptor-γ on Renal Crystal Formation in Hyperoxaluric Rodents |
title_full | Differential Roles of Peroxisome Proliferator-Activated Receptor-α and Receptor-γ on Renal Crystal Formation in Hyperoxaluric Rodents |
title_fullStr | Differential Roles of Peroxisome Proliferator-Activated Receptor-α and Receptor-γ on Renal Crystal Formation in Hyperoxaluric Rodents |
title_full_unstemmed | Differential Roles of Peroxisome Proliferator-Activated Receptor-α and Receptor-γ on Renal Crystal Formation in Hyperoxaluric Rodents |
title_short | Differential Roles of Peroxisome Proliferator-Activated Receptor-α and Receptor-γ on Renal Crystal Formation in Hyperoxaluric Rodents |
title_sort | differential roles of peroxisome proliferator-activated receptor-α and receptor-γ on renal crystal formation in hyperoxaluric rodents |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4789040/ https://www.ncbi.nlm.nih.gov/pubmed/27022389 http://dx.doi.org/10.1155/2016/9605890 |
work_keys_str_mv | AT taguchikazumi differentialrolesofperoxisomeproliferatoractivatedreceptoraandreceptorgonrenalcrystalformationinhyperoxaluricrodents AT okadaatsushi differentialrolesofperoxisomeproliferatoractivatedreceptoraandreceptorgonrenalcrystalformationinhyperoxaluricrodents AT hamamotoshuzo differentialrolesofperoxisomeproliferatoractivatedreceptoraandreceptorgonrenalcrystalformationinhyperoxaluricrodents AT unnorei differentialrolesofperoxisomeproliferatoractivatedreceptoraandreceptorgonrenalcrystalformationinhyperoxaluricrodents AT kobayashitakahiro differentialrolesofperoxisomeproliferatoractivatedreceptoraandreceptorgonrenalcrystalformationinhyperoxaluricrodents AT andoryosuke differentialrolesofperoxisomeproliferatoractivatedreceptoraandreceptorgonrenalcrystalformationinhyperoxaluricrodents AT tozawakeiichi differentialrolesofperoxisomeproliferatoractivatedreceptoraandreceptorgonrenalcrystalformationinhyperoxaluricrodents AT gaobing differentialrolesofperoxisomeproliferatoractivatedreceptoraandreceptorgonrenalcrystalformationinhyperoxaluricrodents AT kohrikenjiro differentialrolesofperoxisomeproliferatoractivatedreceptoraandreceptorgonrenalcrystalformationinhyperoxaluricrodents AT yasuitakahiro differentialrolesofperoxisomeproliferatoractivatedreceptoraandreceptorgonrenalcrystalformationinhyperoxaluricrodents |