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.