Mechanisms regulating invasiveness and growth of endometriosis lesions in rat experimental model and in humans

Sotnikova, N. Yu.; Antsiferova, Yulia S.; Posiseeva, L. V.; Shishkov, Dmitrii N.; Posiseev, Denis V.; Филиппова, Е. С.

doi:10.1016/j.fertnstert.2009.11.024

Cited by 30 publications

(25 citation statements)

References 19 publications

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“…TGF-β is highly expressed in the endometrium and is secreted by endometrial glands and macrophages [32], [70]. Patients with endometriosis have higher levels of TGF-β1 in the peritoneal fluid compared to disease-free subjects [10], [71] and higher TGF-β2 mRNA expression was reported in the ectopic endometriotic lesions [72]. In our study, LXA 4 differentially regulated TGF-β isoforms.…”

Section: Discussionsupporting

confidence: 52%

Lipoxin A4 Prevents the Progression of De Novo and Established Endometriosis in a Mouse Model by Attenuating Prostaglandin E2 Production and Estrogen Signaling

et al. 2014

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Endometriosis, a leading cause of pelvic pain and infertility, is characterized by ectopic growth of endometrial-like tissue and affects approximately 176 million women worldwide. The pathophysiology involves inflammatory and angiogenic mediators as well as estrogen-mediated signaling and novel, improved therapeutics targeting these pathways are necessary. The aim of this study was to investigate mechanisms leading to the establishment and progression of endometriosis as well as the effect of local treatment with Lipoxin A4 (LXA4), an anti-inflammatory and pro-resolving lipid mediator that we have recently characterized as an estrogen receptor agonist. LXA4 treatment significantly reduced endometriotic lesion size and downregulated the pro-inflammatory cytokines IL-1β and IL-6, as well as the angiogenic factor VEGF. LXA4 also inhibited COX-2 expression in both endometriotic lesions and peritoneal fluid cells, resulting in attenuated peritoneal fluid Prostaglandin E2 (PGE2) levels. Besides its anti-inflammatory effects, LXA4 differentially regulated the expression and activity of the matrix remodeling enzyme matrix metalloproteinase (MMP)-9 as well as modulating transforming growth factor (TGF)-β isoform expression within endometriotic lesions and in peritoneal fluid cells. We also report for first time that LXA4 attenuated aromatase expression, estrogen signaling and estrogen-regulated genes implicated in cellular proliferation in a mouse model of disease. These effects were observed both when LXA4 was administered prior to disease induction and during established disease. Collectively, our findings highlight potential targets for the treatment of endometriosis and suggest a pleotropic effect of LXA4 on disease progression, by attenuating pro-inflammatory and angiogenic mediators, matrix remodeling enzymes, estrogen metabolism and signaling, as well as downstream proliferative pathways.

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Section: Discussionsupporting

confidence: 52%

Lipoxin A4 Prevents the Progression of De Novo and Established Endometriosis in a Mouse Model by Attenuating Prostaglandin E2 Production and Estrogen Signaling

et al. 2014

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“…Recent studies have demonstrated that the content of MMP-1, MMP-2, and MMP-7 in the peritoneal fluid of women, with endometriosis is increased in comparison to that of healthy women, and the level of their inhibitors (TIMPs), on the contrary, is reduced [38]. Our earlier investigations have showed the imbalance of MMPs and their inhibitors synthesis in the endometrial tissue of women with endometriosis as well as during the development of experimental endometriosis in rats [39]. However, according to the literature data, production of MMP-9 by macrophages of women with endometriosis is suppressed.…”

Section: Resultsmentioning

confidence: 99%

Different Effects of the Immunomodulatory Drug GMDP Immobilized onto Aminopropyl Modified and Unmodified Mesoporous Silica Nanoparticles upon Peritoneal Macrophages of Women with Endometriosis

Antsiferova

Sotnikova

Parfenyuk

2013

BioMed Research International

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The aim of the present work was to compare in vitro the possibility of application of unmodified silica nanoparticles (UMNPs) and modified by aminopropyl groups silica nanoparticles (AMNPs) for topical delivery of immunomodulatory drug GMDP to the peritoneal macrophages of women with endometriosis. The absence of cytotoxic effect and high cellular uptake was demonstrated for both types of silica nanoparticles. The immobilization of GMDP on the UMNPs led to the suppression of the stimulatory effect of GMDP on the membrane expression of scavenger receptors SR-AI and SR-B, mRNAs expression of NOD2 and RAGE, and synthesis of proteolytic enzyme MMP-9 and its inhibitor TIMP-1. GMDP, immobilized onto AMNPs, enhanced the initially reduced membrane expression of SRs and increased NOD2, RAGE, and MMP-9 mRNAs expression by macrophages. Simultaneously high level of mRNAs expression of factors, preventing undesirable hyperactivation of peritoneal macrophages (SOCS1 and TIMP-1), was observed in macrophages incubated in the presence of GMDP, immobilized onto AMNPs. The effect of AMNPs immobilized GMDP in some cases exceeded the effect of free GMDP. Thus, among the studied types of silica nanoparticles, AMNPs are the most suitable nanoparticles for topical delivery of GMDP to the peritoneal macrophages.

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“…Compared to healthy women, TGF-β levels are elevated in the peritoneal fluid of women with endometriosis (Oosterlynck et al 1994; Kupker et al 1998); elevated TGF-β induces fibrosis, increasing the formation of endometriotic adhesions in the peritoneum (Chegini 2008). TGFB2 mRNA levels are increased in the endometriotic lesions of women and in a rat model of endometriosis (Sotnikova et al 2010). Further evidence shows that TGF-β signaling increases endometriotic lesion growth by transcriptional activation of KLF11 (Correa et al 2016).…”

Section: Tgf-β Family Signaling and Female Reproductive Tract Diseasesmentioning

confidence: 99%

The TGF-β Family in the Reproductive Tract

Monsivais

Matzuk

Pangas

2017

Cold Spring Harb Perspect Biol

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The transforming growth factor β (TGF-β) family has a profound impact on the reproductive function of various organisms. In this review, we discuss how highly conserved members of the TGF-β family influence the reproductive function across several species. We briefly discuss how TGF-β-related proteins balance germ-cell proliferation and differentiation as well as dauer entry and exit in Caenorhabditis elegans. In Drosophila melanogaster, TGF-β-related proteins maintain germ stem-cell identity and eggshell patterning. We then provide an in-depth analysis of landmark studies performed using transgenic mouse models and discuss how these data have uncovered basic developmental aspects of male and female reproductive development. In particular, we discuss the roles of the various TGF-β family ligands and receptors in primordial germ-cell development, sexual differentiation, and gonadal cell development. We also discuss how mutant mouse studies showed the contribution of TGF-β family signaling to embryonic and postnatal testis and ovarian development. We conclude the review by describing data obtained from human studies, which highlight the importance of the TGF-β family in normal female reproductive fnction during pregnancy and in various gynecologic pathologies.

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Mechanisms regulating invasiveness and growth of endometriosis lesions in rat experimental model and in humans

Cited by 30 publications

References 19 publications

Lipoxin A4 Prevents the Progression of De Novo and Established Endometriosis in a Mouse Model by Attenuating Prostaglandin E2 Production and Estrogen Signaling

Lipoxin A4 Prevents the Progression of De Novo and Established Endometriosis in a Mouse Model by Attenuating Prostaglandin E2 Production and Estrogen Signaling

Different Effects of the Immunomodulatory Drug GMDP Immobilized onto Aminopropyl Modified and Unmodified Mesoporous Silica Nanoparticles upon Peritoneal Macrophages of Women with Endometriosis

The TGF-β Family in the Reproductive Tract

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