Sphingosine-1-phosphate induces COX-2 expression and PGE2 production in human granulosa cells through a S1P₁/₃-mediated YAP signaling Cheng, Jung-Chien; Chang, Hsun-Ming; Liu, Pang-Pin; Leung, P. C. K.
Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid that can regulate various physiological and pathological processes. The expression of S1P has been detected in human follicular fluid. In addition, two S1P receptors, S1P₁ and S1P₃, are expressed at a high level in human granulosa cells. Cyclooxygenase-2 (COX-2)-derived prostaglandin E2 (PGE2) production plays a critical role in the regulation of ovulation. However, thus far, the effect of S1P on COX-2 expression and PGE2 production in human granulosa cells remains unknown. In the present study, our results demonstrated that treatment with S1P significantly induced COX-2, but not COX-1, expression and increased PGE2 production in human granulosa cells. The stimulatory effects of S1P on COX-2 expression and PGE2 production were attenuated by treatment with specific antagonist of S1P₁ or S1P₃ and siRNA-mediated knockdown of S1P₁ or S1P₃. In addition, the COX-2 expression was induced by S1P₁ or S1P₃ agonist treatment. Interestingly, treatment with S1P activated YAP signaling via S1P₁ and S1P₃. Moreover, knockdown of YAP partially attenuated S1P-induced COX-2 expression and PGE2 production. These results provide evidence that S1P induces COX-2 expression and PGE2 production in human granulosa cells through a S1P₁/₃-mediated YAP signaling pathway.
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