Université de Liège Réseau des Bibliothèques

Serveur institutionnel des thèses de doctorat

Nouvelles thèses
dans BICTEL/e - ULg
  • Kreusch, Marie - Graded-commutative nonassociative algebras: higher octonions and Krichever-Novikov superalgebras; their structures, combinatorics and non-trivial cocycles.
  • Simon, Ronnie Ernst - Lattice dynamics in antimony and tellurium based phase-change materials
  • Belleflamme, Alexandre - Detection of past and future atmospheric circulation changes over the North Atlantic region with the help of an automatic circulation type classification
Présentation Recherche thèse Dépôt thèse Accès
Page de résumé pour ULgetd-03142012-102455

Auteur : Dubail, Johanne
E-mail de l'auteur : Johanne.Dubail@student.ulg.ac.be
URN : ULgetd-03142012-102455
Langue : Anglais/English
Titre : Role of ADAMTS2, 3 and 14 in physiological and pathological processes
Intitulé du diplôme : Doctorat en sciences biomédicales et pharmaceutiques
Département : Médecine - Département des sciences précliniques
Jury :
Nom : Titre :
CATALDO, Didier Membre du jury/Committee Member
MICHIELS, Carine Membre du jury/Committee Member
MOALI, Catherine Membre du jury/Committee Member
MUNAUT, Carine Membre du jury/Committee Member
NOEL, Agnès Membre du jury/Committee Member
STRUMAN, Ingrid Membre du jury/Committee Member
COLIGE , Alain Promoteur/Director
Mots-clés :
  • connective tissues/tissus conjonctifs
  • aminoprocollagen peptidase/aminoprocollagène peptidase
  • angiogenesis/angiogenèse
  • knock-out mouse/souris déficientes
Date de soutenance : 2012-03-21
Type d'accès : Restreint/Intranet
Résumé :

Enzymes of the ADAMTS family are closely related to MMPs and ADAMs. They further contain specific domains, such as a variable number of a domain known as « ThromboSPondin type I repeats » (TSP I).

Amongs this family, ADAMTS2, 3 and 14 share a strong homology of sequence and structure. The primary function of ADAMTS2, 3 and 14, also known as aminoprocollagen peptidases, is to process fibrillar procollagen into mature molecules by excising the amino-propeptide. The lack of activity of ADAMTS2 is responsible for a inherited disease in human and in animal (Ehlers Danlos syndrom type VII C or dermatosparaxis) characterized by an extreme skin fragility. Analysis of ADAMTS-2 knock-out mice (Adamts2-/-) has shown also that male are sterile, suggesting that ADAMTS-2 have functions independent of its aminoprocollagen peptidase activity.

In the first part of the results, we demonstrate that ADAMTS-2 inhibits angiogenesis, independently of its catalytic activity. ADAMTS-2 is able to reduce proliferation of endothelial cells, and to induce their retraction and detachment from the substrate resulting in apoptosis. Dephosphorylation of Erk1/2 and MLC largely precedes the ADAMTS-2 induced morphological alterations. In 3-D culture models, ADAMTS-2 strongly reduced branching of capillary-like structures formed by endothelial cells and their long-term maintenance and inhibited vessels formation in embryoid bodies (EB). Growth and vascularization of tumors formed in nude mice by HEK 293-EBNA cells expressing ADAMTS-2 were drastically reduced. A similar anti-tumoral activity was observed when using cells expressing recombinant deleted forms of ADAMTS-2, including catalytically inactive enzyme. Nucleolin, a nuclear protein also found to be associated with the cell membrane, was identified as a potential receptor mediating the antiangiogenic properties of ADAMTS-2.

In following parts of results, we studied the functions of ADAMTS2, 3 and 14 in two different models: zebrafish models and mice models without expression of one of the aminoprocollagen peptidases.

Zebrafish models: Four orthologues for ADAMTS2, 3 and 14 were identified in zebrafish (two orthologues for ADAMTS-2, one for ADAMTS3 and one for ADAMTS14). These enzymes present each a specific expression profil in RT-PCR and in situ hybridization studies. ADAMTS3 is the most expressed during the embryonic period. In situ hybridization demonstrate a strong expression of ADAMTS3 in the neural tube and in specific parts of the brains, suggesting a function during brain development. Repression of ADAMTS-3 expression by specific morpholinos induces lethality at an early stage of development.

Mice models: Constitutive knock-out of Adamts3 lead to embryonic lethality around 15 dpc. Histological studies of 12.5 dpc, 13.5 dpc and 14.5 dpc Adamts3-/- embryos demonstrated an implication of Adamts3 in development of the brain, the liver and most probably of the heart.

Constitutive knock-out of Adamts14 lead to a reduction of body size and of ear size. Histological studies of Adamts14-/- bones and ears suggested an implication of Adamts14 in growth regulation of bones and/or cartilage.

Autre version :
Fichiers :
Nom du fichier Taille Temps de chargement évalué (HH:MI:SS)
Modem 56K ADSL
Pas de fichier trouvé.
Fichiers accessibles par l'Internet [Public/Internet] ou que par l'Intranet [Restreint/Intranet].

Bien que le maximum ait été fait pour que les droits des ayants-droits soient respectés, si un de ceux-ci constatait qu'une oeuvre sur laquelle il a des droits a été utilisée dans BICTEL/e ULg sans son autorisation explicite, il est invité à prendre contact le plus rapidement possible avec la Direction du Réseau des Bibliothèques.

Parcourir BICTEL/e par Auteur|Département | Rechercher dans BICTEL/e

© Réseau des Bibliothèques de l'ULg, Grande traverse, 12 B37 4000 LIEGE