Prostaglandin E2 increases cardiac fibroblast proliferation and increases cyclin D expression via EP1 receptor

SummaryPGE2 affects growth of many cell types. Thus, we hypothesized that PGE2 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 PGE2 receptor (EPs) mRNAs in NVF. Using flow cytometry, we found that PGE2 decreased the percentage of cells in G0/G1 and increased the number of cells in S phase. PGE2 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 PGE2 increased phosphorylation of p42/44 MAPK and Akt and that PGE2-stimulation of cyclin D3 was antagonized with both a MEK inhibitor and a PI3 kinase inhibitor. In conclusion, PGE2 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.