title: Sphingosine-1-phosphate induces COX-2 expression and PGE2 production in human granulosa cells through a S1P1/3-mediated YAP signaling.
abstract: 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.
authors.affiliation: Department of Obstetrics and Gynaecology, Child & Family Research Institute, University of British Columbia, Vancouver, British Columbia V5Z 4H4, Canada.
authors.forename: Jung-Chien
authors.initials: JC
authors.lastname: Cheng
authors.affiliation: Department of Obstetrics and Gynaecology, Child & Family Research Institute, University of British Columbia, Vancouver, British Columbia V5Z 4H4, Canada.
authors.forename: Hsun-Ming
authors.initials: HM
authors.lastname: Chang
authors.affiliation: Department of Obstetrics and Gynaecology, Child & Family Research Institute, University of British Columbia, Vancouver, British Columbia V5Z 4H4, Canada; Department of Obstetrics and Gynaecology, E-DA Hospital, Kaohsiung 82445, Taiwan.
authors.forename: Pang-Pin
authors.initials: PP
authors.lastname: Liu
authors.affiliation: Department of Obstetrics and Gynaecology, Child & Family Research Institute, University of British Columbia, Vancouver, British Columbia V5Z 4H4, Canada. Electronic address: peter.leung@ubc.ca.
authors.forename: Peter C K
authors.initials: PC
authors.lastname: Leung
mesh_terms: D018797:Cell Cycle Proteins; D002460:Cell Line; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000096:biosynthesis* / Q000235:genetics; D015232:Dinoprostone / Q000096:biosynthesis*; D005260:Female; D015870:Gene Expression; D006107:Granulosa Cells / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D008246:Lysophospholipids / Q000502:physiology*; D009687:Nuclear Proteins / Q000378:metabolism*; D049349:Receptors, Lysosphingolipid / Q000378:metabolism; D015398:Signal Transduction; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000502:physiology; D000081025:Sphingosine-1-Phosphate Receptors; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D008246:Lysophospholipids; D009687:Nuclear Proteins; D049349:Receptors, Lysosphingolipid; C477362:S1PR1 protein, human; D000081025:Sphingosine-1-Phosphate Receptors; D014157:Transcription Factors; C456659:YY1AP1 protein, human; C577483:sphingosine-1-phosphate receptor-3, human; C060506:sphingosine 1-phosphate; D051546:Cyclooxygenase 2; D015232:Dinoprostone; D013110:Sphingosine
keywords: COX-2; Granulosa cells; PGE2; S1P; YAP