Matrix metalloproteinase-2, membranous type 1 matrix metalloproteinase, and tissue inhibitor of metalloproteinase-2 expression in ectopic and eutopic endometrium
ABSTRACT To investigate expression of matrix metalloproteinase-2 (MMP-2), membranous type 1 matrix metalloproteinase (MT1-MMP), and tissue inhibitor of metalloproteinase-2 (TIMP-2) in ectopic and eutopic endometrium from women with and without endometriosis throughout the menstrual cycle.
Molecular studies in human tissue.
Reproductive immunology laboratory of a university medical center.
Fifty-three premenopausal woman (23 with endometriosis and 30 without endometriosis) undergoing laparoscopic surgery. Endometrium and ectopic endometriosis tissue were obtained at the time of surgery.
Messenger RNA and protein expression from eutopic and ectopic endometrium was analyzed by using quantitative competitive polymerase chain reaction, zymography, and Western blot assay.
Uterine endometrium from women with endometriosis expressed higher levels of MMP-2 and MT1-MMP and lower levels of TIMP-2 than did endometrium from normal women.
Eutopic endometrium from patients with endometriosis may be more invasive and prone to peritoneal implantation because of greater expression of MMP-2 and MT1-MMP and lower expression of TIMP-2 messenger RNA, compared with endometrium from women without endometriosis. Thus, increased proteolytic activity may help to explain the invasive factors that result in endometriosis.
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ABSTRACT: Prostaglandin E2 (PGE2) plays an important role in the pathogenesis of endometriosis. We recently reported that inhibition of COX-2 decreased migration as well as invasion of human endometriotic epithelial and stromal cells. Results of the present study indicates that selective inhibition of PGE2 receptors EP2 and EP4 suppresses expression and/or activity of MMP1, MMP2, MMP3, MMP7 and MMP9 proteins and increases expression of TIMP1, TIMP2, TIMP3, and TIMP4 proteins and thereby decreases migration and invasion of human immortalized endometriotic epithelial and stromal cells into matrigel. The interactions between EP2/EP4 and MMPs are mediated through Src and β-arrestin 1 protein complex involving MT1-MMP and EMMPRIN in human endometriotic cells. These novel findings provide an important molecular and cellular framework for further evaluation of selective inhibition of EP2 and EP4 as potential nonsteroidal therapy for endometriosis in childbearing-age women.Molecular and Cellular Endocrinology 01/2011; 332(1-2):306-13. DOI:10.1016/j.mce.2010.11.022 · 4.24 Impact Factor
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ABSTRACT: Recent studies have shown that the local expression of soluble interleukin (IL) -1 receptor type II (sIL-1 RII) in endometrial tissue of women with endometriosis is decreased, and the depression of IL-1 RII was more significant in infertile women than that in fertile women with endometriosis. In this research, we investigated the remedial effect of sIL-1-RII administration on endometriosis in the nude mouse model. NINETEEN NUDE MODEL MICE WITH ENDOMETRIOSIS WERE RANDOMLY DIVIDED INTO THREE GROUPS: group A was treated by intraperitoneal administration with only sIL-1 RII for two weeks, group B was similarly treated with only IL-1, and group C (control) was administered saline . After 2 weeks, the size of the ectopic endometrial lesions was calculated, and the expression of vascular endothelial growth factor (VEGF) and B-cell lymphoma leukemia-2 (Bcl-2) were detected by immunohistochemistry. The IL-8 and VEGF levels in the peritoneal fluid (PF) and serum were also measured by enzyme-linked immunosorbent assay (ELISA). The mean size of ectopic endometrial lesion did not differ between the three groups (P > 0.05). Compared with the control, the expression of VEGF and Bcl-2 was significantly lower in group A, and higher in group B. In the three groups, the levels of IL-8 in the PF and serum were highest in group A, and lowest in group B. sIL-1 RII may suppresse hyperplasia of ectopic endometriosis, perhaps by reducing the expression of certain cytokines, such as VEGF, IL-8, and Bcl-2, which could provide a new clinical strategy for the treatment of endometriosis.01/2010; 24(1):43-50. DOI:10.1016/S1674-8301(10)60007-3
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ABSTRACT: The CC chemokines, regulated on activation, normal T-cell expressed and secreted (RANTES) and macrophage-inflammatory protein-1alpha (MIP-1alpha), have been identified as potential contributors to the pathogenesis and the progression of endometriosis. Dioxin, an air pollutant, and estrogen also appear to be involved in endometriosis. The aim of this study was to probe into the effect of dioxin and estrogen on expression of the chemokines in endometriosis-associated cells, and to explore the pathogenesis of endometriosis. Co-culture models were established to evaluate the secretion of human RANTES and MIP-1alpha. The effects of a dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD) and estrogen on the invasion of endometrial stromal cells (ESC) were also examined by using an invasion assay, and the translation and proteolytic activity of matrix metalloproteinase (MMP)-9 and MMP-2 in ESC were determined by western blot and zymography, respectively. Our results showed that the combination of 17beta-estradiol and TCDD increased the secretion of RANTES and MIP-1alpha, promoted the invasiveness of ESC and increased the expression of MMP-2 and MMP-9 in ESC. Anti-RANTES, anti-MIP-1alpha neutralizing antibody or antibody against their receptors could effectively inhibit the invasiveness of ESC and the expression of MMP-2 and MMP-9. The combination of 17beta-estradiol with TCDD may facilitate the onset of endometriosis and contribute to its development by increasing the invasion of ESC mediated by CC-motif chemokines.Human Reproduction 08/2008; 23(7):1614-26. DOI:10.1093/humrep/den125 · 4.59 Impact Factor