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Global Gene Expression Profiling in PPAR-γ Agonist-Treated Kidneys in an Orthologous Rat Model of Human Autosomal Recessive Polycystic Kidney Disease
Kidneys are enlarged by aberrant proliferation of tubule epithelial cells leading to the formation of numerous cysts, nephron loss, and interstitial fibrosis in polycystic kidney disease (PKD). Pioglitazone (PIO), a PPAR-γ agonist, decreased cell proliferation, interstitial fibrosis, and inflammatio...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi Publishing Corporation
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3359747/ https://www.ncbi.nlm.nih.gov/pubmed/22666229 http://dx.doi.org/10.1155/2012/695898 |
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author | Yoshihara, Daisuke Kugita, Masanori Yamaguchi, Tamio Aukema, Harold M. Kurahashi, Hiroki Morita, Miwa Hiki, Yoshiyuki Calvet, James P. Wallace, Darren P. Toyohara, Takafumi Abe, Takaaki Nagao, Shizuko |
author_facet | Yoshihara, Daisuke Kugita, Masanori Yamaguchi, Tamio Aukema, Harold M. Kurahashi, Hiroki Morita, Miwa Hiki, Yoshiyuki Calvet, James P. Wallace, Darren P. Toyohara, Takafumi Abe, Takaaki Nagao, Shizuko |
author_sort | Yoshihara, Daisuke |
collection | PubMed |
description | Kidneys are enlarged by aberrant proliferation of tubule epithelial cells leading to the formation of numerous cysts, nephron loss, and interstitial fibrosis in polycystic kidney disease (PKD). Pioglitazone (PIO), a PPAR-γ agonist, decreased cell proliferation, interstitial fibrosis, and inflammation, and ameliorated PKD progression in PCK rats (Am. J. Physiol.-Renal, 2011). To explore genetic mechanisms involved, changes in global gene expression were analyzed. By Gene Set Enrichment Analysis of 30655 genes, 13 of the top 20 downregulated gene ontology biological process gene sets and six of the top 20 curated gene set canonical pathways identified to be downregulated by PIOtreatment were related to cell cycle and proliferation, including EGF, PDGF and JNK pathways. Their relevant pathways were identified using the Kyoto Encyclopedia of Gene and Genomes database. Stearoyl-coenzyme A desaturase 1 is a key enzyme in fatty acid metabolism found in the top 5 genes downregulated by PIO treatment. Immunohistochemical analysis revealed that the gene product of this enzyme was highly expressed in PCK kidneys and decreased by PIO. These data show that PIO alters the expression of genes involved in cell cycle progression, cell proliferation, and fatty acid metabolism. |
format | Online Article Text |
id | pubmed-3359747 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-33597472012-06-04 Global Gene Expression Profiling in PPAR-γ Agonist-Treated Kidneys in an Orthologous Rat Model of Human Autosomal Recessive Polycystic Kidney Disease Yoshihara, Daisuke Kugita, Masanori Yamaguchi, Tamio Aukema, Harold M. Kurahashi, Hiroki Morita, Miwa Hiki, Yoshiyuki Calvet, James P. Wallace, Darren P. Toyohara, Takafumi Abe, Takaaki Nagao, Shizuko PPAR Res Research Article Kidneys are enlarged by aberrant proliferation of tubule epithelial cells leading to the formation of numerous cysts, nephron loss, and interstitial fibrosis in polycystic kidney disease (PKD). Pioglitazone (PIO), a PPAR-γ agonist, decreased cell proliferation, interstitial fibrosis, and inflammation, and ameliorated PKD progression in PCK rats (Am. J. Physiol.-Renal, 2011). To explore genetic mechanisms involved, changes in global gene expression were analyzed. By Gene Set Enrichment Analysis of 30655 genes, 13 of the top 20 downregulated gene ontology biological process gene sets and six of the top 20 curated gene set canonical pathways identified to be downregulated by PIOtreatment were related to cell cycle and proliferation, including EGF, PDGF and JNK pathways. Their relevant pathways were identified using the Kyoto Encyclopedia of Gene and Genomes database. Stearoyl-coenzyme A desaturase 1 is a key enzyme in fatty acid metabolism found in the top 5 genes downregulated by PIO treatment. Immunohistochemical analysis revealed that the gene product of this enzyme was highly expressed in PCK kidneys and decreased by PIO. These data show that PIO alters the expression of genes involved in cell cycle progression, cell proliferation, and fatty acid metabolism. Hindawi Publishing Corporation 2012 2012-05-13 /pmc/articles/PMC3359747/ /pubmed/22666229 http://dx.doi.org/10.1155/2012/695898 Text en Copyright © 2012 Daisuke Yoshihara et al. https://creativecommons.org/licenses/by/3.0/ 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 Yoshihara, Daisuke Kugita, Masanori Yamaguchi, Tamio Aukema, Harold M. Kurahashi, Hiroki Morita, Miwa Hiki, Yoshiyuki Calvet, James P. Wallace, Darren P. Toyohara, Takafumi Abe, Takaaki Nagao, Shizuko Global Gene Expression Profiling in PPAR-γ Agonist-Treated Kidneys in an Orthologous Rat Model of Human Autosomal Recessive Polycystic Kidney Disease |
title | Global Gene Expression Profiling in PPAR-γ Agonist-Treated Kidneys in an Orthologous Rat Model of Human Autosomal Recessive Polycystic Kidney Disease |
title_full | Global Gene Expression Profiling in PPAR-γ Agonist-Treated Kidneys in an Orthologous Rat Model of Human Autosomal Recessive Polycystic Kidney Disease |
title_fullStr | Global Gene Expression Profiling in PPAR-γ Agonist-Treated Kidneys in an Orthologous Rat Model of Human Autosomal Recessive Polycystic Kidney Disease |
title_full_unstemmed | Global Gene Expression Profiling in PPAR-γ Agonist-Treated Kidneys in an Orthologous Rat Model of Human Autosomal Recessive Polycystic Kidney Disease |
title_short | Global Gene Expression Profiling in PPAR-γ Agonist-Treated Kidneys in an Orthologous Rat Model of Human Autosomal Recessive Polycystic Kidney Disease |
title_sort | global gene expression profiling in ppar-γ agonist-treated kidneys in an orthologous rat model of human autosomal recessive polycystic kidney disease |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3359747/ https://www.ncbi.nlm.nih.gov/pubmed/22666229 http://dx.doi.org/10.1155/2012/695898 |
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