PGE2 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. © 2011 Elsevier Ltd.
Harding, P., & LaPointe, M. C. (2011). Prostaglandin E2 increases cardiac fibroblast proliferation and increases cyclin D expression via EP1 receptor. Prostaglandins Leukotrienes and Essential Fatty Acids, 84(5–6), 147–152. https://doi.org/10.1016/j.plefa.2011.01.003