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...
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| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2012-01-01
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| Series: | PPAR Research |
| Online Access: | http://dx.doi.org/10.1155/2012/695898 |
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| author | Daisuke Yoshihara Masanori Kugita Tamio Yamaguchi Harold M. Aukema Hiroki Kurahashi Miwa Morita Yoshiyuki Hiki James P. Calvet Darren P. Wallace Takafumi Toyohara Takaaki Abe Shizuko Nagao |
| author_facet | Daisuke Yoshihara Masanori Kugita Tamio Yamaguchi Harold M. Aukema Hiroki Kurahashi Miwa Morita Yoshiyuki Hiki James P. Calvet Darren P. Wallace Takafumi Toyohara Takaaki Abe Shizuko Nagao |
| author_sort | Daisuke Yoshihara |
| collection | DOAJ |
| 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 | Article |
| id | doaj-art-90d8d1327d6349b79a6de18f141726c5 |
| institution | Kabale University |
| issn | 1687-4757 1687-4765 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | PPAR Research |
| spelling | doaj-art-90d8d1327d6349b79a6de18f141726c52025-02-03T06:13:28ZengWileyPPAR Research1687-47571687-47652012-01-01201210.1155/2012/695898695898Global Gene Expression Profiling in PPAR-γ Agonist-Treated Kidneys in an Orthologous Rat Model of Human Autosomal Recessive Polycystic Kidney DiseaseDaisuke Yoshihara0Masanori Kugita1Tamio Yamaguchi2Harold M. Aukema3Hiroki Kurahashi4Miwa Morita5Yoshiyuki Hiki6James P. Calvet7Darren P. Wallace8Takafumi Toyohara9Takaaki Abe10Shizuko Nagao11Education and Research Center of Animal Models for Human Diseases, Fujita Health University, Toyoake, Aichi 4701192, JapanEducation and Research Center of Animal Models for Human Diseases, Fujita Health University, Toyoake, Aichi 4701192, JapanEducation and Research Center of Animal Models for Human Diseases, Fujita Health University, Toyoake, Aichi 4701192, JapanDepartment of Human Nutritional Sciences, University of Manitoba, Winnipeg, MB, R3T 2N2, CanadaDivision of Molecular Genetics, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Aichi 4701192, JapanEducation and Research Center of Animal Models for Human Diseases, Fujita Health University, Toyoake, Aichi 4701192, JapanSchool of Health Sciences, Fujita Health University, Toyoake, Aichi 4701192, JapanThe Kidney Institute, University of Kansas Medical Center, Kansas City, KS 66160, USAThe Kidney Institute, University of Kansas Medical Center, Kansas City, KS 66160, USADepartment of Clinical Biology and Hormonal Regulation, Tohoku University Graduate School of Biomedical Engineering, Sendai, Miyagi 9808574, JapanDepartment of Clinical Biology and Hormonal Regulation, Tohoku University Graduate School of Biomedical Engineering, Sendai, Miyagi 9808574, JapanEducation and Research Center of Animal Models for Human Diseases, Fujita Health University, Toyoake, Aichi 4701192, JapanKidneys 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.http://dx.doi.org/10.1155/2012/695898 |
| spellingShingle | Daisuke Yoshihara Masanori Kugita Tamio Yamaguchi Harold M. Aukema Hiroki Kurahashi Miwa Morita Yoshiyuki Hiki James P. Calvet Darren P. Wallace Takafumi Toyohara Takaaki Abe Shizuko Nagao Global Gene Expression Profiling in PPAR-γ Agonist-Treated Kidneys in an Orthologous Rat Model of Human Autosomal Recessive Polycystic Kidney Disease PPAR Research |
| 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 |
| url | http://dx.doi.org/10.1155/2012/695898 |
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