Global Gene Expression Profiling in PPAR-γ Agonist-Treated Kidneys in an Orthologous Rat Model of Human Autosomal Recessive Polycystic Kidney Disease

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dc.contributor.authorYoshihara, Daisuke
dc.contributor.authorKugita, Masanori
dc.contributor.authorYamaguchi, Tamio
dc.contributor.authorAukema, Harold M.
dc.contributor.authorKurahashi, Hiroki
dc.contributor.authorMorita, Miwa
dc.contributor.authorHiki, Yoshiyuki
dc.contributor.authorCalvet, James P.
dc.contributor.authorWallace, Darren P.
dc.contributor.authorToyohara, Takafumi
dc.contributor.authorAbe, Takaaki
dc.contributor.authorNagao, Shizuko
dc.date.accessioned2015-05-14T16:29:25Z
dc.date.available2015-05-14T16:29:25Z
dc.date.issued2012-5-13
dc.date.updated2015-03-29T13:31:20Z
dc.description.abstractKidneys 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.
dc.description.versionPeer Reviewed
dc.identifier.citationDaisuke Yoshihara, Masanori Kugita, Tamio Yamaguchi, et al., “Global Gene Expression Profiling in PPAR-γ Agonist-Treated Kidneys in an Orthologous Rat Model of Human Autosomal Recessive Polycystic Kidney Disease,” PPAR Research, vol. 2012, Article ID 695898, 10 pages, 2012. doi:10.1155/2012/695898
dc.identifier.urihttp://dx.doi.org/10.1155/2012/695898
dc.identifier.urihttp://hdl.handle.net/1993/30494
dc.language.rfc3066en
dc.rightsopen accessen_US
dc.rights.holderCopyright © 2012 Daisuke Yoshihara 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.
dc.titleGlobal Gene Expression Profiling in PPAR-γ Agonist-Treated Kidneys in an Orthologous Rat Model of Human Autosomal Recessive Polycystic Kidney Disease
dc.typeJournal Article
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