PMID:21668646

Citation	Ueno, T and Fujimori, K (2011) Novel suppression mechanism operating in early phase of adipogenesis by positive feedback loop for enhancement of cyclooxygenase-2 expression through prostaglandin F2α receptor mediated activation of MEK/ERK-CREB cascade. FEBS J. 278:2901-12
Abstract	Prostaglandin (PG) F(2α) suppresses adipocyte differentiation by inhibiting the function of peroxisome proliferator-activated receptor γ. In this study, we identified a novel suppression mechanism, operating in the early phase of adipogenesis, that increased the production of anti-adipogenic PGF(2α) and PGE(2) by enhancing cyclooxygenase (COX) 2 expression through the PGF(2α) -activated FP receptor/extracellular-signal-regulated kinase (ERK)/cyclic AMP response element binding protein (CREB) cascade. COX-2 expression was enhanced with a peak at 1 h for the mRNA level and at 3 h for the protein level after the addition of Fluprostenol, an FP receptor agonist. The Fluprostenol-derived elevation of COX-2 expression was suppressed by the co-treatment with an FP receptor antagonist, AL8810, with a mitogen-activated protein kinase (MEK; ERK kinase) inhibitor, PD98059. ERK was phosphorylated within 10 min after the addition of Fluprostenol, and its phosphorylation was inhibited by the co-treatment with AL8810 or PD98059. Moreover, FP receptor mediated activation of the MEK/ERK cascade and COX-2 expression increased the production of PGF(2α) and PGE(2) . An FP receptor antagonist and each inhibitor for MEK and COX-2 suppressed the PGF(2α) -derived induction of synthesis of these PGs. Furthermore, promoter-luciferase and chromatin immunoprecipitation assays demonstrated that PGF(2α) -derived COX-2 expression was activated through binding of CREB to the promoter region of the COX-2 gene in 3T3-L1 cells. These results indicate that PGF(2α) suppresses the progression of the early phase of adipogenesis by enhancing the binding of CREB to the COX-2 promoter via FP receptor activated MEK/ERK cascade. Thus, PGF(2α) forms a positive feedback loop that coordinately suppresses the early phase of adipogenesis through the increased production of anti-adipogenic PGF(2α) and PGE(2) .
Links	PubMed Online version:10.1111/j.1742-4658.2011.08213.x
Keywords	3T3-L1 Cells; Adipogenesis/drug effects; Animals; Cyclic AMP Response Element-Binding Protein/metabolism; Cyclooxygenase 2/genetics; Dinoprost/biosynthesis; Dinoprostone/biosynthesis; Extracellular Signal-Regulated MAP Kinases/physiology; Feedback; Mice; Mitogen-Activated Protein Kinase 1/metabolism; Mitogen-Activated Protein Kinase 3/metabolism; Mitogen-Activated Protein Kinase Kinases/metabolism; PPAR gamma/metabolism; Prostaglandins F, Synthetic/pharmacology; Receptors, Prostaglandin/physiology; Signal Transduction/physiology
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:PF2R	involved_in	GO:0010628: positive regulation of gene expression	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:PF2R		GO:0010628: positive regulation of gene expression	ECO:0000314:		P		Expression of COX-2 Figure 1 B	complete CACAO 2464

References

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