Activin A upregulates PTGS2 expression and increases PGE2 production in human granulosa-lutein cells.
Activin A is one of the members of transforming growth factor-β superfamily that is expressed in human large luteal cells, and may act in an autocrine/paracrine manner to regulate luteal function. Prostaglandin-endoperoxide synthase 2 (PTGS2) enzyme and its derivative, prostaglandin E2 (PGE2), play significant roles in the regulation of corpus luteum formation and maintenance. To date, whether activin A can induce the expression of PTGS2 and the production of PGE2 in human granulosa-lutein cells is largely unknown. The aim of this study was to examine the effects of activin A on the regulation of PTGS2 expression and PGE2 production in human granulosa-lutein cells, and to investigate the underlying signal transduction mechanisms. In this study, the immortalized (SVOG cells) and primary human granulosa-lutein cells were used as the cell models. A TGF-β/activin type I receptor inhibitor, SB431542 and small interfering RNAs were used to investigate the activin A-induced downstream signaling pathway. We have demonstrated that activin A upregulated the expression of PTGS2 and increased the production of PGE2 via an ACVR1B-mediated SMAD2/3-SMAD4 signaling pathway. Our results suggest that activin A may be involved in the modulation of human corpus luteum formation via the induction of PTGS2 expression and PGE2 production.
Department of Obstetrics and GynaecologyChild and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.|Department of Obstetrics and GynaecologyE-DA Hospital, Kaohsiung, Taiwan.
Pang-Pin
PP
Liu
Department of Obstetrics and GynaecologyChild and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.
Hsun-Ming
HM
Chang
Department of Obstetrics and GynaecologyChild and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.
Jung-Chien
JC
Cheng
Department of Obstetrics and GynaecologyChild and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada peter.leung@ubc.ca.
Peter C K
PC
Leung
D028341:Activins / Q000494:pharmacology*; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006107:Granulosa Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008184:Luteal Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015854:Up-Regulation
C422405:activin A; D028341:Activins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D015232:Dinoprostone