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

研究成果: Article査読

10 被引用数 (Scopus)

抄録

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.

本文言語English
論文番号695898
ジャーナルPPAR Research
DOI
出版ステータスPublished - 2012

All Science Journal Classification (ASJC) codes

  • 創薬
  • 薬理学(医学)

フィンガープリント

「Global gene expression profiling in PPAR-γ agonist-treated kidneys in an orthologous rat model of human autosomal recessive polycystic kidney disease」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル