Sphingosine pathway deregulation in endometriotic tissues
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This paper investigated alterations in the sphingosine pathway within endometriotic tissues, identifying key dysregulations.
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Abstract
OBJECTIVE: To investigate key genes expression of the sphingosine-1-phosphate pathway in endometriotic tissues.
DESIGN: A case-control laboratory study.
SETTING: Tertiary care university hospital.
PATIENT(S): A total of 31 women, with (n = 16) and without (n = 15) endometriosis took part in the study.
INTERVENTION(S): After surgical excision with pathological analysis, endometrial specimens were obtained from women affected or not by endometriosis.
MAIN OUTCOME MEASURE(S): SPHK1-2, SGPP1-2, SGPL1, SPHKAP, and S1PR1-5 messenger RNA expression by quantitative real-time polymerase chain reaction (PCR) in the endometrium of 15 disease-free women, 16 eutopic and 16 ectopic endometrium of endometriosis-affected women. The S1PR1 and S1PR2 expression were further investigated by immunohistochemistry.
RESULT(S): The SGPP2 expression was decreased in eutopic and ectopic endometrium of endometriosis-affected women (1.7- and 16.7-fold, respectively). The SGPP1, weakly expressed in healthy endometrium, is up-regulated in endometriosis-affected women (11.9- and 64.7-fold, respectively), but its expression remains low. The SGPL1 expression was decreased in ectopic endometrium (3.3-fold) and SPHKAP expression was increased in ectopic endometrium (112.6-fold) compared with endometrium of disease-free women. In endometriosis-affected women, S1PR3 expression was decreased in eutopic and ectopic endometrium (2.1- and 6.3-fold, respectively); S1PR2 and S1PR1 expression was increased in eutopic (2.5-fold) and ectopic endometrium (2.6-fold). These increases were confirmed at the protein levels by immunohistochemistry.
CONCLUSION(S): Expression of the enzymes implicated in the regulation of the sphingosine-1-phosphate level balance and of its receptors is overall heavily deregulated in endometriotic lesions in favor of a decreased sphingosine-1-phosphate catabolism. Our results plead for a role of the sphingosine pathway in establishing and survival of endometriotic lesions.
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Cited by (42)
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- Sphingosine 1-phosphate elicits a ROS-mediated proinflammatory response in human endometrial stromal cells via ERK5 activation 2023
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- Antilipidemic ezetimibe induces regression of endometriotic explants in a rat model of endometriosis with its anti-inflammatory and anti-angiogenic effects 2022
- PPARγ Agonists: Emergent Therapy in Endometriosis 2021
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- Curcumin and Endometriosis 2020
- Sphingosine 1-phosphate receptors are dysregulated in endometriosis: possible implication in transforming growth factor β-induced fibrosis 2020
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- Hormones and Inflammation: An Update on Endometriosis 2019
- The role of inflammation, oxidative stress, angiogenesis, and apoptosis in the pathophysiology of endometriosis: Basic science and new insights based on gene expression 2019
- Sphingosine 1 Phosphate (S1P) Increased IL-6 Expression and Cell Growth in Endometriotic Cells 2019
- The Role of Oxidative Stress and Membrane Transport Systems during Endometriosis: A Fresh Look at a Busy Corner 2018
- Reduced α-2,6 sialylation regulates cell migration in endometriosis 2018
- Alteration of Nrf2 and Glutamate Cysteine Ligase expression contribute to lesions growth and fibrogenesis in ectopic endometriosis 2017
- Differential expression of EWI-2 in endometriosis, its functional role and underlying molecular mechanisms 2017
- Lipidomic profiling of endometrial fluid in women with ovarian endometriosis† 2017
- The Clinical Significance of Endocannabinoids in Endometriosis Pain Management 2017
- Role of the protein kinase BRAF in the pathogenesis of endometriosis 2016
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- The differential expression of mRNAs and long noncoding RNAs between ectopic and eutopic endometria provides new insights into adenomyosis 2015
- Inhibition of MAPK and VEGFR by Sorafenib Controls the Progression of Endometriosis 2015
- MAP kinases and the inflammatory signaling cascade as targets for the treatment of endometriosis? 2015
- Pathogenetic Mechanisms of Deep Infiltrating Endometriosis 2015
- Endometriosis also affects the decidua in contact with the fetal membranes during pregnancy 2014
- Protein oxidative stress markers in peritoneal fluids of women with deep infiltrating endometriosis are increased 2014
- Dysregulated sphingolipid metabolism in endometriosis 2014
- An update on the pharmacological management of endometriosis 2013
- Hormonal therapy deregulates prostaglandin-endoperoxidase synthase 2 (PTGS2) expression in endometriotic tissues 2013
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