The inducible prostaglandin E synthase mPGES-1 regulates growth of endometrial tissues and angiogenesis in a mouse implantation model
The inducible prostaglandin E synthase mPGES-1 regulates growth of endometrial tissues and angiogenesis in a mouse implantation model
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DOI：
10.1016/j.biopha.2010.12.008
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发表时间：
2011-02-01
影响因子：
7.5
通讯作者：
Majima, Masataka
中科院分区：
文献类型：
--
作者：
Numao, Akiko;Hosono, Kanako;Majima, Masataka
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 (mPGES1 (/) -> 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. (C) 2010 Published by Elsevier Masson SAS.
