Lipoxin A₄ prevents the progression of de novo and established endometriosis in a mouse model by attenuating prostaglandin E₂ production and estrogen signaling
| العنوان: | Lipoxin A₄ prevents the progression of de novo and established endometriosis in a mouse model by attenuating prostaglandin E₂ production and estrogen signaling |
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| المؤلفون: | Rajesh, Kumar, Anne-Catherine, Clerc, Ilaria, Gori, Ronan, Russell, Chiara, Pellegrini, Lerisa, Govender, Jean-Christophe, Wyss, Dela, Golshayan, Geraldine O, Canny |
| المصدر: | Plos One, vol. 9, no. 2, pp. e89742 PLoS ONE, Vol 9, Iss 2, p e89742 (2014) PLoS ONE |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Vascular Endothelial Growth Factor A, Drugs and Devices, Anatomy and Physiology, Drug Research and Development, Science, Interleukin-1beta, Immunology, Endometriosis, Gene Expression, Real-Time Polymerase Chain Reaction, Dinoprostone, Molecular Genetics, Mice, Aromatase, Endocrinology, Animals, Biology, DNA Primers, Analysis of Variance, Interleukin-6, Reproductive System, Computational Biology, Obstetrics and Gynecology, Estrogens, Immunohistochemistry, Biosynthetic Pathways, Lipoxins, Mice, Inbred C57BL, Cyclooxygenase 2, Medicine, Female, Signal Transduction, Research Article |
| الوصف: | 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. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=pmid_dedup__::a4ed9f0aba826f678a9e1bbd793dc45e https://serval.unil.ch/notice/serval:BIB_FAC47D58EF03 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.pmid.dedup....a4ed9f0aba826f678a9e1bbd793dc45e |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |