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


Authors: 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
Article Title: Global Gene Expression Profiling in PPAR-γ Agonist-Treated Kidneys in an Orthologous Rat Model of Human Autosomal Recessive Polycystic Kidney Disease
Alternate Title: PPAR research
Journal Title: PPAR research
Volume: 2012
ISSN: 1687-4765
Publisher: Unknown  
Date Published: 2012
DOI/URL:
Notes: 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.
KUMC Authors
  1. James Calvet
    90 Calvet
  2. Darren Wallace
    61 Wallace
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