The inducible prostaglandin E synthase mPGES-1 regulates growth of endometrial tissues and angiogenesis in a mouse implantation model

Akiko Numao, Numao A, Kanako Hosono, Hosono K, Tatsunori Suzuki, Suzuki T, Izumi Hayashi, Hayashi I, Satoshi Uematsu, Akira S, Shizuo Akira, Yukiko Ogino, Ogino Y, Kawauchi H, Hirohito Kawauchi, Nobuya Unno, Unno N, Masataka Majima, Majima M
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2010 · vol. 65(1) , pp. 77–84 · doi:10.1016/j.biopha.2010.12.008 · PMID:21247731 · W2064322936
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This study investigated the role of the inducible prostaglandin E synthase mPGES-1 in regulating endometrial growth and angiogenesis during mouse implantation.

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Abstract

Endometriosis is one of the most common gynecological diseases in women of reproductive age. Although cyclooxygenase (COX)-2 inhibitors are effective in the treatment of endometriosis, the adverse cardiovascular effects associated with these inhibitors have limited their use. Microsomal prostaglandin E synthase-1 (mPGES-1) is an inducible enzyme downstream of COX-2 in prostaglandin E(2) biosynthesis. Previously, we developed mPGES-1 knockout mice (mPGES-1(-/-)) and have identified for the first time the roles of ectopic lesion- and host-associated mPGES-1 in angiogenesis and the growth of endometrial tissues. When mPGES-1(-/-) endometrial fragments were implanted into wild type (WT) mice (mPGES-1(-/-)→WT), or WT fragments implanted into mPGES-1(-/-) mice (WT→mPGES-1(-/-)), the growth of the implants was suppressed at days 14 and 28 after implantation, compared toWT→WT transplantation. An even greater degree of suppression was observed in mPGES-1(-/-) endometrial fragments implanted into mPGES-1(-/-) mice (mPGES-1(-/-)→mPGES-1(-/-)). After WT-WT implantation, mPGES-1 expression was localized at the border of the implanted endometrial tissues. Microvessel density, determined by CD31 immunostaining, was markedly suppressed in the mPGES-1(-/-) endometrial fragments implanted into mPGES-1(-/-) mice, with some suppression also observed in the mPGES-1(-/-)→WT and WT→mPGES-1(-/-) groups. The expression of vascular endothelial growth factor (VEGF-A) was significantly reduced in mPGES-1(-/-) endometrial tissues implanted into mPGES-1(-/-) mice at days 14 and 28, in comparison to the WT→WT group. These results suggested that mPGES-1 enhanced angiogenesis and growth of the endometrial implant, and indicate that mPGES-1 may be a good therapeutic target for endometriosis.

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Condition tags

endometriosis

MeSH descriptors

Endometrium Endometrium Intramolecular Oxidoreductases Neovascularization, Physiologic Neovascularization, Physiologic Animals Animals Cyclooxygenase 2 Cyclooxygenase 2 Cyclooxygenase 2 Endometriosis Endometriosis Endometriosis Endometrium Endometrium Female Female Intramolecular Oxidoreductases Intramolecular Oxidoreductases Mice

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