Microarray evaluation of EP4 receptor-mediated prostaglandin E2 suppression of 3T3-L1 adipocyte differentiation.
Prostaglandin E(2) (PGE(2)) has been shown to negatively regulate adipogenesis. To explore to what extent PGE(2) inhibits the differentiation of cells to adipocytes and to examine whether its effect could be due to EP4 receptor signaling, we used microarrays to analyze the gene expression profiles of 3T3-L1 cells exposed to a differentiation cocktail supplemented with PGE(2), AE1-329 (an EP4 agonist), or vehicle. The differentiation-associated responses in genes such as adipocytokines and enzymes related to lipid metabolism were largely weakened upon PGE(2) treatment. In particular, the expression of peroxisome proliferator activated receptor-gamma and CCAAT/enhancer binding protein-alpha, genes playing a central role in adipogenesis, was greatly suppressed. PGE(2) appears to be ineffective to a subclass of insulin target genes such as hexokinase 2 and phosphofructokinase. Similar responses were produced in the differentiation-associated genes upon AE1-329 treatment. These results suggest that PGE(2) inhibits a crucial step of the adipocyte differentiation process by acting on the EP4 receptor in 3T3-L1 cells.
Sugimoto
Yukihiko
Y
Department of Physiological Chemistry, Kyoto University Graduate School of Pharmaceutical Sciences, Sakyo-ku, Kyoto 606-8501, Japan.
Tsuboi
Hiroaki
H
Okuno
Yasushi
Y
Tamba
Shigero
S
Tsuchiya
Soken
S
Tsujimoto
Gozo
G
Ichikawa
Atsushi
A
D016475:3T3 Cells; D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects*; D015232:Dinoprostone / Q000494:pharmacology*; D004798:Enzymes / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D008738:Methyl Ethers / Q000494:pharmacology; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D011506:Proteins / Q000235:genetics; D018078:Receptors, Prostaglandin E / Q000235:genetics*; D058309:Receptors, Prostaglandin E, EP4 Subtype
D004798:Enzymes; D008738:Methyl Ethers; C461399:ONO-AE1-329; D011506:Proteins; C545651:Ptger4 protein, mouse; D018078:Receptors, Prostaglandin E; D058309:Receptors, Prostaglandin E, EP4 Subtype; D003994:Bucladesine; D015232:Dinoprostone