NRF2/GCL pathway in endometriosis Abstract ID : 1685 Soumis par : Louis MARCELLIN Le 2016-03-14 21:43:05 Nom de la catégorie : SEUD CONGRESS Typologie : Communication orale / Oral communication Statut : validé Autorisation de diffusion : Yes/Oui ------------------------------------endogenous antioxidant effect that protect against oxidative damage triggered by inflammation, as a main part in the first steps of the development of endometriosis lesion. Glutamate cysteine ligase (GCL), a target gene of NRF2, is the first enzyme in the synthesis cascade of glutathione, an important endogenous antioxidant. Materials /Patients and methods: We conduct a case-control laboratory study in a tertiary-care university from 2012 to 2014 to investigate whether the expression of NRF2 and GCL are deregulated in endometriotic tissues. Fitfty-one patients were recruited for the study: 26 with histologically proven endometriosis and 25 unaffected women. A thorough surgical examination of the abdominopelvic cavity was performed on all of the study participants. mRNA expressions of NRF2 and GCL were investigated by quantitative RT-PCR in endometrium of disease-free women, and eutopic and ectopic endometrium from endometriosis-affected women. Ex vivo stromal and epithelial cells were extracted from endometrial and endometriotic biopsies from an another sets of patients to explore expression of NRF2 and GCL in this both stromal and epithelial compartment. Expressions were further explored by immunohistochemistry in endometrium of disease-free women and eutopic and ectopic endometrium of endometriosis-affected women. Peritoneal horn implants from wild type black6 mice and from NRF2 -/- mice were compared and studied in histology. Results: We found a mRNA levels of NRF2 and GCL significantly lower in ectopic endometrium of endometriosisaffected women (p<0.001 and p<0.05, respectively). The western blot analysis of primary cultures cells revealed a significant decreased o the expression of NRF2 and GCL in ectopic lesion in the epithelial cells (p<0.05) but not in the stroma cells. The immunohistochemical analysis revealed a decreased staining in ectopic endometriotic tissues with specific antibodies. The mean volume of ectopic horn implants was higher in case of NRF2 -/- (p<0.05) with a significant increased staining for the red Sirius (p<0.05). Conclusion: These findings indicate that expression of the transcription factor NRF2 and its effector GCL are both heavily deregulated in endometriotic lesions. ------------------------------------Mots clefs : endometriosis, NRF2, GCL, oxidative stress Auteurs : Références : , , , Auteurs Louis Marcellin 1, Pietro Santulli 1, Sandrine Chouzenoux 2, Carole Nicco 2, Olivier CERCLES 2, Charles Chapron 1, Frédéric Batteux 2, 1. Hôpital Universitaire Paris Centre (HUPC), Centre Hospitalier Universitaire (CHU) CochinService de Chirurgie Gynécologie Obstétrique II et Médecine de la Reproduction, Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, Paris, FRANCE 2. Equipe Stress Oxydant, Prolifération Cellulaire et Inflammation, Département Développement, Reproduction, Cancer,, Inserm U1016, Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, Paris, FRANCE Auteurs (raw format) Marcellin Louis - email : [email protected] Etablissement : Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine Service : Hôpital Universitaire Paris Centre (HUPC), Centre Hospitalier Universitaire (CHU) CochinService de Chirurgie Gynécologie Obstétrique II et Médecine de la Reproduction Ville : Paris Pays : FRANCE Présentateur : Oui Santulli Pietro - email : [email protected] Etablissement : Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine Service : Hôpital Universitaire Paris Centre (HUPC), Centre Hospitalier Universitaire (CHU) CochinService de Chirurgie Gynécologie Obstétrique II et Médecine de la Reproduction Ville : Paris Pays : FRANCE Présentateur : Non Chouzenoux Sandrine - email : [email protected] Etablissement : Inserm U1016, Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine Service : Equipe Stress Oxydant, Prolifération Cellulaire et Inflammation, Département Développement, Reproduction, Cancer, Ville : Paris Pays : FRANCE Présentateur : Non Nicco Carole - email : [email protected] Etablissement : Inserm U1016, Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine Service : Equipe Stress Oxydant, Prolifération Cellulaire et Inflammation, Département Développement, Reproduction, Cancer, Ville : Paris Pays : FRANCE Présentateur : Non CERCLES Olivier - email : [email protected] Etablissement : Inserm U1016, Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine Service : Equipe Stress Oxydant, Prolifération Cellulaire et Inflammation, Département Développement, Reproduction, Cancer, Ville : Paris Pays : FRANCE Présentateur : Non Chapron Charles - email : [email protected] Etablissement : Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine Service : Hôpital Universitaire Paris Centre (HUPC), Centre Hospitalier Universitaire (CHU) CochinService de Chirurgie Gynécologie Obstétrique II et Médecine de la Reproduction Ville : Paris Pays : FRANCE Présentateur : Non Batteux Frédéric - email : [email protected] Etablissement : Inserm U1016, Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine Service : Equipe Stress Oxydant, Prolifération Cellulaire et Inflammation, Département Développement, Reproduction, Cancer, Ville : Paris Pays : FRANCE Présentateur : Non