Prostaglandin E 2 Induces FGF‐9 Expression in Human Endometriotic Stromal Cells

Fibroblast Growth Factor‐9 (FGF‐9) is a mitogen and survival factor for nerve and mesenchymal cells. Previously, we reported that FGF‐9 and its high affinity receptors were induced by estrogen (E 2 ) in the endometriotic lesion. Since prostaglandin E 2 (PGE 2 ) is a potent inducer for E 2 production and the expression of FGF‐9 is E 2 ‐dependent, we sought to determine roles of PGE 2 in the regulation of FGF‐9 in endometriotic stromal cells. Administration of PGE 2 markedly increased FGF‐9 mRNA expression, which was not inhibited by pretreatment with ER antagonist, ICI182,870, indicating an E 2 ‐independent pathway may be existed. Treatment of the cells with PGE 2 enhanced FGF‐9 mRNA expression which was blocked by pre‐treatment with MEK inhibitor, PKC inhibitor, or calcium/calmodulin dependent kinase inhibitor but not by the PKA inhibitor or PI 3 kinase inhibitor. PGE 2 caused rapid and transient elevation of intracellular Ca 2+ concentration, phosphorylation of PKC α/β II , PKC δ, PKC γ, and ERK1/2 in endometriotic stromal cell. Transient transfection with si_PKCδ or dominant negative ERK1/2 blocked the induction of FGF‐9 expression mediated by PGE 2 . Further study demonstrated that EP3 agonist, sulprostone, exerted similar inductive effect as that by PGE 2 . These data indicated that PGE 2 directly regulates FGF9 gene expression via EP 3 ‐mediated signaling pathway, which is parallel to PGE 2 ‐indued E 2 production in human endometriotic stromal cell.