TGF-β1 Induces COX-2 Expression and PGE2 Production in Human Granulosa Cells Through Smad Signaling Pathways (original) (raw)
Journal Article
1Reproductive Medical Center (L.F., Y.-P.S.), The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China 450052
2Department of Obstetrics and Gynaecology (L.F., H.-M.C., J.-C.C., P.C.K.L.), Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada V5Z 4H4
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2Department of Obstetrics and Gynaecology (L.F., H.-M.C., J.-C.C., P.C.K.L.), Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada V5Z 4H4
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2Department of Obstetrics and Gynaecology (L.F., H.-M.C., J.-C.C., P.C.K.L.), Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada V5Z 4H4
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2Department of Obstetrics and Gynaecology (L.F., H.-M.C., J.-C.C., P.C.K.L.), Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada V5Z 4H4
*Address all correspondence and requests for reprints to: Peter C. K. Leung, PhD, FCAHS, FRSC, Department of Obstetrics and Gynaecology, Child and Family Research Institute, University of British Columbia, Room 317, 950 West 28th Avenue, Vancouver, British Columbia, Canada V5Z 4H4; or Ying-Pu Sun, MD, PhD, Center for Reproductive Medicine, The First Affiliated Hospital of Zhengzhou University, 40 Daxue Road, Zhengzhou, Henan, China 450052.
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1Reproductive Medical Center (L.F., Y.-P.S.), The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China 450052
*Address all correspondence and requests for reprints to: Peter C. K. Leung, PhD, FCAHS, FRSC, Department of Obstetrics and Gynaecology, Child and Family Research Institute, University of British Columbia, Room 317, 950 West 28th Avenue, Vancouver, British Columbia, Canada V5Z 4H4; or Ying-Pu Sun, MD, PhD, Center for Reproductive Medicine, The First Affiliated Hospital of Zhengzhou University, 40 Daxue Road, Zhengzhou, Henan, China 450052.
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Received:
13 November 2013
Cite
Lanlan Fang, Hsun-Ming Chang, Jung-Chien Cheng, Peter C. K. Leung, Ying-Pu Sun, TGF-β1 Induces COX-2 Expression and PGE2 Production in Human Granulosa Cells Through Smad Signaling Pathways, The Journal of Clinical Endocrinology & Metabolism, Volume 99, Issue 7, 1 July 2014, Pages E1217–E1226, https://doi.org/10.1210/jc.2013-4100
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Context:
Cyclooxygenase-2 (COX-2) expression and prostaglandin E2 (PGE2) production have been shown to play key roles in the regulation of ovulation. The TGF-β superfamily members are important molecules that regulate many ovarian functions under normal physiological and pathological conditions. TGF-β1 and its receptors are expressed in human granulosa cells. However, to date, whether TGF-β1 can regulate COX-2 expression and PGE2 production, which in turn contribute to the process of ovulation, remains unknown.
Objective:
The objective of the study was to investigate the effects of TGF-β1 on COX-2 expression and PGE2 production in human granulosa cells.
Design:
SVOG cells are human granulosa cells that were obtained from women undergoing in vitro fertilization and immortalized with Simian virus 40 large T antigen. SVOG cells were used to investigate the effect of TGF-β1 on COX-2 expression and PGE2 production.
Setting:
The study was conducted at an academic research center.
Main Outcome Measures:
mRNA and protein levels were examined by RT-quantitative real-time PCR and Western blotting, respectively. The concentrations of PGE2 in the culture medium were measured by an ELISA.
Results:
TGF-β1 treatment induced COX-2 expression and PGE2 production. The inductive effects of TGF-β1 on COX-2 and PGE2 were abolished by the inhibition of TGF-β type I receptor (TβRI). In addition, treatment with TGF-β1 activated phosphorylated mothers against decapentaplegic (Smad)-2 and Smad3 signaling pathways. Inhibition of the Smad signaling pathways by small interfering RNA-mediated approaches attenuated the TGF-β1-induced COX-2 expression and PGE2 production.
Conclusion:
TGF-β1 induced PGE2 production by inducing the COX-2 expression through a Smad-dependent signaling pathway in human granulosa cells.
Copyright © 2014 by the Endocrine Society
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