VEGF-B prevents excessive angiogenesis by inhibiting FGF2/FGFR1 pathway.
Signal Transduct Target Ther
; 8(1): 305, 2023 08 18.
Article
em En
| MEDLINE
| ID: mdl-37591843
ABSTRACT
Although VEGF-B was discovered as a VEGF-A homolog a long time ago, the angiogenic effect of VEGF-B remains poorly understood with limited and diverse findings from different groups. Notwithstanding, drugs that inhibit VEGF-B together with other VEGF family members are being used to treat patients with various neovascular diseases. It is therefore critical to have a better understanding of the angiogenic effect of VEGF-B and the underlying mechanisms. Using comprehensive in vitro and in vivo methods and models, we reveal here for the first time an unexpected and surprising function of VEGF-B as an endogenous inhibitor of angiogenesis by inhibiting the FGF2/FGFR1 pathway when the latter is abundantly expressed. Mechanistically, we unveil that VEGF-B binds to FGFR1, induces FGFR1/VEGFR1 complex formation, and suppresses FGF2-induced Erk activation, and inhibits FGF2-driven angiogenesis and tumor growth. Our work uncovers a previously unrecognized novel function of VEGF-B in tethering the FGF2/FGFR1 pathway. Given the anti-angiogenic nature of VEGF-B under conditions of high FGF2/FGFR1 levels, caution is warranted when modulating VEGF-B activity to treat neovascular diseases.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fator 2 de Crescimento de Fibroblastos
/
Fator B de Crescimento do Endotélio Vascular
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Signal Transduct Target Ther
Ano de publicação:
2023
Tipo de documento:
Article