title: Prostaglandin E2 increases cardiac fibroblast proliferation and increases cyclin D expression via EP1 receptor.
abstract: PGE(2) affects growth of many cell types. Thus, we hypothesized that PGE(2) would stimulate growth of cardiac fibroblasts. To test our hypothesis we used neonatal rat ventricular fibroblasts (NVF). RT-PCR demonstrated the presence of all 4 PGE(2) receptor (EPs) mRNAs in NVF. Using flow cytometry, we found that PGE(2) decreased the percentage of cells in G0/G1 and increased the number of cells in S phase. PGE(2) also increased expression of cyclin D3, a known regulator of the cell cycle and this effect was mimicked by the EP1/EP3 agonist sulprostone. Next, we found that treatment of NVF with PGE(2) increased phosphorylation of p42/44 MAPK and Akt and that PGE(2)-stimulation of cyclin D3 was antagonized with both a MEK inhibitor and a PI3 kinase inhibitor. In conclusion, PGE(2) stimulates cardiac fibroblast proliferation via EP1 and/or EP3, p42/44 MAPK and Akt-regulation of cyclin D3. These results may be relevant to cardiac fibrosis.
authors.affiliation: Hypertension and Vascular Research Division, Department of Internal Medicine, Henry Ford Hospital, Detroit, MI 48202, USA. phardin1@hfhs.org
authors.forename: Pamela
authors.initials: P
authors.lastname: Harding
authors.forename: Margot C
authors.initials: MC
authors.lastname: LaPointe
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D056741:Cyclin D / Q000235:genetics* / Q000378:metabolism; D015232:Dinoprostone / Q000494:pharmacology*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009206:Myocardium / Q000166:cytology*; D051381:Rats; D058306:Receptors, Prostaglandin E, EP1 Subtype / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D056741:Cyclin D; D058306:Receptors, Prostaglandin E, EP1 Subtype; D015232:Dinoprostone