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Titre : | Effets des anticorps neutralisants lactivation du tgfB; dans un modèle murin de sclerodermie et de fibrose |
Auteurs : | Francine Laurie GUEFACK TIOPAC, Auteur ; François Huaux, Promoteur |
Type de document : | Travail de fin d'études |
Editeur : | Bruxelles : Institut Paul Lambin, 2020 |
Langues: | Français |
Index. décimale : | TFE - Biologie médicale |
Résumé : |
Systemic sclerosis (SSc) is an idiopathic systemic autoimmune disease characterized by immune dysfunction and fibrosis in lung and skin. This disease can be mimicked in animals by administrating bleomycin, a cytotoxic antibiotic used in the treatment of some cancers.
This model in C57BL / 6 mice is largely used to study of SSc disease, understand the mechanisms responsible for fibrosis and propose new therapeutic interventions. The current immunopathogenesis of fibrosis in SSc comprise the activation and recruitment of immune cells which release cytokine and growth factors that directly stimulate fibroblasts and matrix protein deposition. Among those factors, TGFβ is central in the fibrotic process. Its activation from latent TGFβ1 depends on integrins (αVβ8) but also on GARP. Monoclonal antibodies directed against the GARP / TGF-β1 complexes thus represent an attractive approach to reduce experimental SSc and fibrosis. The purpose of this study was to determine whether inhibition of TGF-b and GARP reduced the skin and lung fibrosis in bleomycin-induced SSc in mice. To achieve this objectif, we treated mice with antibodies neutralizing TGF and GARP. Next, we tried to analyze and quantify the development of fibrosis using a digital and histological quantification after Sirius red (SR) staining. SR allows to highlight the collagen fibers in polarized microscopy. The 2IP imaging platform (IREC) has developed an automated analysis method for digital images. This method calculates the surface of collagen stained by RS on pulmonary and cutaneous scanned sections. The quantification is based on light refraction by different maturation grades of collagen fibers (red, yellow-orange and green) in the tissue. This digital imaging method would have allowed us to quantify the fibrotic alterations induced by bleomycin in the presence of neutralizing antibodies GARP and TGFβ. We performed the animal experimental part of this project and collected and conditioned all lung and skin samples. Unfortunately, SR stainings and quantifications were not performed because of the covid crisis. |
Accès : | Identifiez-vous avant d'accéder au document électronique |
Disponible en ligne : | Oui |
Lieu du stage : | UCL - Louvain center for Toxicologyand Applied Pharmacology(LTAP) - Institut de Recherche Expérimentale et Clinique (IREC) |
Département : | Biologie médicale |
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TFE biologie médicale Adobe Acrobat PDF |