期刊
PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS
卷 84, 期 5-6, 页码 147-152出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.plefa.2011.01.003
关键词
Prostaglandin E2; Fibroblast; Cyclin D; Proliferation
资金
- National Institutes of Health [P01 HL-28982]
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. (C) 2011 Elsevier Ltd. All rights reserved.
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