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

Numao, Akiko; Hosono, Kanako; Suzuki, Tatsunori; Hayashi, Izumi; Uematsu, Satoshi; Akira, Shizuo; Ogino, Yukiko; Kawauchi, Hirohito; Unno, Nobuya; Murakami, Masataka

doi:10.1016/j.biopha.2010.12.008

Cited by 23 publications

(20 citation statements)

References 39 publications

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“…Intriguingly, overexpression or elevated activity of phospholipase(s) and terminal PG synthase(s) is found in endometriotic lesions and macrophages (20)(21)(22)92) (Figure 2, right panel). In a mouse implantation model, both endometrial fragments from microsomal PGE synthase-1 knockout (mPGES-1-KO) donor to wild type recipient and endometrial fragment from wild type © 1996-2015 donor to mPGES-1-KO recipient show reduced size of endometriotic lesion compared to wild type to wild type transplantation (93), supporting the idea that terminal PG synthase is crucial to the development of endometriosis. Regarding the regulation of PLA 2 and PGES, several lines of evidence have indicated that hypoxia is a key inducer (94)(95)(96)(97) and thus it is reasonable to rationalize that hypoxic environment causes the elevated levels of PGs in peritoneal cavity (Figure 2, right panel).…”

Section: Interaction Between Hypoxia and Pgsmentioning

confidence: 89%

Pathological functions of hypoxia in endometriosis

Hsiao

Lin

et al. 2015

Front Biosci

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Endometriosis is one of the most common gynecological diseases that significantly reduce the life quality of affected women. Research results from the past decade clearly demonstrated that aberrant production of estrogen and cyclooxygenase-2-derived prostaglandin E2 play indispensable roles in the pathogenesis of this disease. However, the etiology of endometriosis remains obscure. Recent evidence reveals a new facet of endometriotic pathogenesis by showing that hypoxia induces the expression of many important downstream genes to regulate the implantation, survival, and maintenance of ectopic endometriotic lesions. These new findings shed lights on future investigations of delineating the etiology of endometriosis and designing new therapeutic strategy for endometriosis.

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Section: Interaction Between Hypoxia and Pgsmentioning

confidence: 89%

Pathological functions of hypoxia in endometriosis

Hsiao

Lin

et al. 2015

Front Biosci

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“…26 Cumulative evidences have declared that deficiency of Cox-2 or mPGES-1 caused a reduction in uterine Vegf mRNA level. 28,29 Vegf was a well-known angiogenesis promoter and could profoundly influence the uterine angiogenesis which was crucial to decidualization. 28,30 In fact, Hmgn1 could also direct the expression of Vegf in the uterine stromal cells undergoing decidualization.…”

Section: Discussionmentioning

confidence: 99%

Hmgn1 acts downstream of C/EBPβ to regulate the decidualization of uterine stromal cells in mice

Yang

Guo

et al. 2015

Cell Cycle

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“…It has been previously reported that Cox‐2 also participated in uterine angiogenesis during decidualization owing to this evidence that in Cox‐2 deficient mice, one cause of decidualization failure was the deregulated vascular events (Dey et al., ; Matsumoto et al., ; Wang & Dey, ). Additionally, as an inducible enzyme downstream of Cox‐2 in the biosynthesis of prostaglandin E2 which was crucial for uterine decidualization, mPGES‐1 was also implicated in uterine angiogenesis (Kennedy, Gillio‐Meina, & Phang, ; Numao et al., ). The present data indicated that Egr2 could induce the expression of Cox‐2 , mPGES‐1 and Vegf , suggesting a role of Egr2 in uterine angiogenesis during decidualization.…”

Section: Discussionmentioning

confidence: 99%

Egr2 mediates the differentiation of mouse uterine stromal cells responsiveness to HB‐EGF during decidualization

Yue

Yang

et al. 2018

J Exp Zool Pt B

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Although Egr2 is involved in regulating the folliculogenesis and ovulation, there is almost no data describing its physiological function in embryo implantation and decidualization. Here, we showed that Egr2 mRNA was distinctly accumulated in subluminal stromal cells around implanting blastocyst on day 5 of pregnancy as well as in estrogen-activated implantation uterus. Estrogen induced the expression of Egr2 in uterine epithelia. Elevated expression of Egr2 mRNA was also observed in the decidual cells. Silencing of Egr2 by specific siRNA weakened the proliferation of uterine stromal cells and reduced the expression of Ccnd1, Ccnd3, Cdk4, and Cdk6. Furthermore, Egr2 advanced the expression of Prl8a2, Prl3c1, and Pgr, the well-established differentiation markers for decidualization. Administration of exogenous recombinant heparin-binding EGF-like growth factor (rHB-EGF) to uterine stromal cells resulted in an increase in the level of Egr2 mRNA. Moreover, siRNA-mediated attenuation of Egr2 impeded the stimulation of HB-EGF on stromal cell differentiation. Knockdown of Egr2 led to a reduction in the expression of Cox-2, mPGES-1, Vegf, Trp53, and Mmp2. Further analysis found that Egr2 may serve as an intermediate to mediate the regulation of HB-EGF on Cox-2, mPGES-1, Vegf, Trp53, Mmp2, and Ccnd3. Collectively, Egr2 may play an important role during embryo implantation and decidualization.

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

Cited by 23 publications

References 39 publications

Pathological functions of hypoxia in endometriosis

Pathological functions of hypoxia in endometriosis

Hmgn1 acts downstream of C/EBPβ to regulate the decidualization of uterine stromal cells in mice

Egr2 mediates the differentiation of mouse uterine stromal cells responsiveness to HB‐EGF during decidualization

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