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Modulation of αVß6 integrin in osteoarthritis-related synovitis and the interaction with VTN(381-397 a.a.) competing for TGF-ß1 activation.
Ciregia, Federica; Deroyer, Céline; Cobraiville, Gaël; Plener, Zelda; Malaise, Olivier; Gillet, Philippe; Fillet, Marianne; Malaise, Michel G; de Seny, Dominique.
Afiliação
  • Ciregia F; Laboratory of Rheumatology, GIGA-I3, University of Liège, CHU de Liège, Liège, Belgium. federica.ciregia@uliege.be.
  • Deroyer C; Laboratory of Rheumatology, GIGA-I3, University of Liège, CHU de Liège, Liège, Belgium.
  • Cobraiville G; Laboratory of Rheumatology, GIGA-I3, University of Liège, CHU de Liège, Liège, Belgium.
  • Plener Z; Laboratory of Rheumatology, GIGA-I3, University of Liège, CHU de Liège, Liège, Belgium.
  • Malaise O; Laboratory of Rheumatology, GIGA-I3, University of Liège, CHU de Liège, Liège, Belgium.
  • Gillet P; Department of Orthopedic Surgery, University Hospital Sart-Tilman, Liege, Belgium.
  • Fillet M; Laboratory for the Analysis of Medicines, CIRM, Department of Pharmacy, University of Liège, Liège, Belgium.
  • Malaise MG; Laboratory of Rheumatology, GIGA-I3, University of Liège, CHU de Liège, Liège, Belgium.
  • de Seny D; Laboratory of Rheumatology, GIGA-I3, University of Liège, CHU de Liège, Liège, Belgium.
Exp Mol Med ; 53(2): 210-222, 2021 02.
Article em En | MEDLINE | ID: mdl-33526813
Osteoarthritis is characterized by structural alteration of joints. Fibrosis of the synovial tissue is often detected and considered one of the main causes of joint stiffness and pain. In our earlier proteomic study, increased levels of vitronectin (VTN) fragment (amino acids 381-397) were observed in the serum of osteoarthritis patients. In this work, the affinity of this fragment for integrins and its putative role in TGF-ß1 activation were investigated. A competition study determined the interaction of VTN(381-397 a.a.) with αVß6 integrin. Subsequently, the presence of αVß6 integrin was substantiated on primary human fibroblast-like synoviocytes (FLSs) by western blot and flow cytometry. By immunohistochemistry, ß6 was detected in synovial membranes, and its expression showed a correlation with tissue fibrosis. Moreover, ß6 expression was increased under TGF-ß1 stimulation; hence, a TGF-ß bioassay was applied. We observed that αVß6 could mediate TGF-ß1 bioavailability and that VTN(381-397 a.a.) could prevent TGF-ß1 activation by interacting with αVß6 in human FLSs and increased α-SMA. Finally, we analyzed serum samples from healthy controls and patients with osteoarthritis and other rheumatic diseases by nano-LC/Chip MS-MS, confirming the increased expression of VTN(381-397 a.a.) in osteoarthritis as well as in lupus erythematosus and systemic sclerosis. These findings corroborate our previous observations concerning the overexpression of VTN(381-397 a.a.) in osteoarthritis but also in other rheumatic diseases. This fragment interacts with αVß6 integrin, a receptor whose expression is increased in FLSs from the osteoarthritic synovial membrane and that can mediate the activation of the TGF-ß1 precursor in human FLSs.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Osteoartrite / Sinovite / Integrinas / Vitronectina / Fator de Crescimento Transformador beta1 / Domínios e Motivos de Interação entre Proteínas / Antígenos de Neoplasias Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Osteoartrite / Sinovite / Integrinas / Vitronectina / Fator de Crescimento Transformador beta1 / Domínios e Motivos de Interação entre Proteínas / Antígenos de Neoplasias Idioma: En Ano de publicação: 2021 Tipo de documento: Article