TGF-β1 Induces COX-2 Expression and PGE2 Production in Human Granulosa Cells Through Smad Signaling Pathways

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Abstract

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.

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