Basic FGF and PDGF-BB synergistically stimulate hyaluronan and IL-6 production by orbital fibroblasts.
Mol Cell Endocrinol
; 433: 94-104, 2016 09 15.
Article
em En
| MEDLINE
| ID: mdl-27267669
ABSTRACT
Orbital fibroblast activation is a central pathologic feature of Graves' Ophthalmopathy (GO). Basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) have been proposed to contribute to GO, but their effects on orbital fibroblasts are largely unknown. We found that bFGF stimulated proliferation and hyaluronan production, but not IL-6 production by orbital fibroblasts, while VEGF hardly affected orbital fibroblast activity. Remarkably, co-stimulation of orbital fibroblasts with bFGF and PDGF-BB synergistically enhanced IL-6 and hyaluronan production and displayed an additive effect on proliferation compared to either bFGF or PDGF-BB stimulation. Nintedanib, a FGF- and PDGF-receptor targeting drug, more efficiently blocked bFGF + PDGF-BB-induced IL-6 and hyaluronan production than dasatinib that only targets PDGF-receptor. In conclusion, bFGF may contribute to orbital inflammation and tissue remodeling in GO, especially through synergistic interaction with PDGF-BB. Multi-target therapy directed at the bFGF and PDGF pathways may potentially be of interest for the treatment of GO.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Interleucina-6
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Proteínas Proto-Oncogênicas c-sis
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Fatores de Crescimento de Fibroblastos
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Fibroblastos
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Ácido Hialurônico
Limite:
Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article