| Titre : | Étude préliminaire à l’évaluation du lien causal entre la dérégulation desmicroARNs199a-3p/-5p et la voie métabolique NOX4-HIF1α-VEGF dans la maladie de Graves-Basedow. |
| Auteurs : | Pénélope COUTURIER, Auteur ; Chantal Dessy, Promoteur ; Julie Craps, Promoteur |
| Type de document : | Travail de fin d'études |
| Editeur : | Bruxelles : Institut Paul Lambin, 2020 |
| Langues: | Français |
| Index. décimale : | TFE - Biologie médicale |
| Résumé : |
Aims:
Graves’ disease is a Th2 autoimmune thyroid disease. The patients produce anti TSH-receptor antibodies which induce hyperthyroidism, goiter, orbitopathy and in more rare cases dermopathy. Graves’ disease is characterized by a rise in oxidative stress and an elevated vascularization. Graves’orbitopathy is the consequence of excessive adipogenesis and fibrosis. As miR199a family is involved in oxidative stress, angiogenesis and adipogenesis, we investigated their role in Graves’ disease context. The laboratory has previously shown that the miR-199a were down-regulated in the pathology. The objective of this study is to better understand the molecular mechanisms involved in the pathology leading to oxidative stress, angiogenesis, and adipogenesis in the thyroid and periorbital adipose tissues. Methods: In vitro thyrocytes model cell line treated with Interleukin-4 were used to mimic Graves’ disease. Human Graves’s orbital fat samples originating from patients presenting exophthalmia due to Graves’ orbitopathy were used. Orbital tissue coming from blepharoplasty were employed as control. Prior analyses, miRs were extracted by Maxwell technic and then transcribed to perform PCR. Proteins of interest were highlighted by western Blot technic, immunohistochemistry and/or immunofluorescence. Results: The results showed that the cultured Htori 3 cells express NIS, DUOX and TPO confirming their status of differentiated thyrocytes. In addition, the validation of the Graves’ model in vitro on the Htori 3 line showed an increase of NOX4, HIF1α, VEGF. The experiments on the quantification of miRs have currently produced no results and need to be repeated. The results obtained from orbital tissues suggested that the regulation of the proteins of interest is directly in the link with the activity of the pathology. TWIST, but not EGR1 was down-regulated suggesting that this transcription factor could participate in the regulation of miR-199a expression in orbital adipose tissue from Graves patients. Conclusion: The Graves’ in vitro thyrocytes model based on HTori3 cells stimulated with Interleukin-4 appears a suitable model to further analyze the pathologic angiogenic and oxidative stress pathways in Graves’ disease. For the second part of this project, although the regulation of proteins associated with angiogenesis and oxidative stress seems associated with the activity of the pathology in periorbital adipose tissue, these results should be verified. |
| Accès : | Identifiez-vous avant d'accéder au document électronique |
| Disponible en ligne : | Oui |
| Lieu du stage : | Université catholique de Louvain - IREC-Pôle de Morphologie (MORF) et Pôle de pharmacologie et Thérapeutique (FATH) |
| Département du TFE : | Biologie médicale |
Documents numériques (1)
 TFE biologie médicale Adobe Acrobat PDF |
