Oligodendrocyte-specific deletion of FGFR2 ameliorates MOG35-55 -induced EAE through ERK and Akt signalling.
Brain Pathol
; 31(2): 297-311, 2021 03.
Article
em En
| MEDLINE
| ID: mdl-33103299
ABSTRACT
Fibroblast growth factors (FGFs) and their receptors (FGFRs) are involved in demyelinating pathologies including multiple sclerosis (MS). In our recent study, oligodendrocyte-specific deletion of FGFR1 resulted in a milder disease course, less inflammation, reduced myelin and axon damage in EAE. The objective of this study was to elucidate the role of oligodendroglial FGFR2 in MOG35-55 -induced EAE. Oligodendrocyte-specific knockout of FGFR2 (Fgfr2ind-/- ) was achieved by application of tamoxifen; EAE was induced using the MOG35-55 peptide. EAE symptoms were monitored over 62 days. Spinal cord tissue was analysed by histology, immunohistochemistry and western blot. Fgfr2ind-/- mice revealed a milder disease course, less myelin damage and enhanced axonal density. The number of oligodendrocytes was not affected in demyelinated areas. However, protein expression of FGFR2, FGF2 and FGF9 was downregulated in Fgfr2ind-/- mice. FGF/FGFR dependent signalling proteins were differentially regulated; pAkt was upregulated and pERK was downregulated in Fgfr2ind-/- mice. The number of CD3(+) T cells, Mac3(+) cells and B220(+) B cells was less in demyelinated lesions of Fgfr2ind-/- mice. Furthermore, expression of IL-1ß, TNF-α and CD200 was less in Fgfr2ind-/- mice than controls. Fgfr2ind-/- mice showed an upregulation of PLP and downregulation of the remyelination inhibitors SEMA3A and TGF-ß expression. These data suggest that cell-specific deletion of FGFR2 in oligodendrocytes has anti-inflammatory and neuroprotective effects accompanied by changes in FGF/FGFR dependent signalling, inflammatory cytokines and expression of remyelination inhibitors. Thus, FGFRs in oligodendrocytes may represent potential targets for the treatment of inflammatory and demyelinating diseases including MS.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Oligodendroglia
/
Sistema de Sinalização das MAP Quinases
/
Encefalomielite Autoimune Experimental
/
Proteínas Proto-Oncogênicas c-akt
/
Receptor Tipo 2 de Fator de Crescimento de Fibroblastos
Limite:
Animals
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article