Global gene expression profiling in PPAR-γ agonist-treated kidneys in an orthologous rat model of human autosomal recessive polycystic kidney disease

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

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number695898
JournalPPAR Research
DOIs
Publication statusPublished - 20-06-2012

Fingerprint

Autosomal Recessive Polycystic Kidney
pioglitazone
Peroxisome Proliferator-Activated Receptors
Gene Expression Profiling
Kidney
Genes
Polycystic Kidney Diseases
Down-Regulation
Cell Proliferation
Cell Cycle
Fibrosis
Fatty Acids
Encyclopedias
Biological Phenomena
Gene Expression
Gene Ontology
MAP Kinase Signaling System
Nephrons
Enzymes
Epidermal Growth Factor

All Science Journal Classification (ASJC) codes

  • Drug Discovery
  • Pharmacology (medical)

Cite this

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. In: PPAR Research. 2012.
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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. / 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.

In: PPAR Research, 20.06.2012.

Research output: Contribution to journalArticle

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AU - Hiki, Yoshiyuki

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AU - Wallace, Darren P.

AU - Toyohara, Takafumi

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AU - Nagao, Shizuko

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