| First Author | Lee C | Year | 2023 |
| Journal | Signal Transduct Target Ther | Volume | 8 |
| Issue | 1 | Pages | 305 |
| PubMed ID | 37591843 | Mgi Jnum | J:339873 |
| Mgi Id | MGI:7524483 | Doi | 10.1038/s41392-023-01539-9 |
| Citation | Lee C, et al. (2023) VEGF-B prevents excessive angiogenesis by inhibiting FGF2/FGFR1 pathway. Signal Transduct Target Ther 8(1):305 |
| abstractText | 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. |
