Volume 8 Issue 9, Sep 2023

ISSN: 2095-9907 

EISSN: 2059-23635 

2023 impact factor 40.8 

 (Clarivate Analytics, 2024)
Volume 8 Issue 9, Sep 2023:
Article
VEGF-B prevents excessive angiogenesis by inhibiting FGF2/FGFR1 pathway
Chunsik Lee  ORCID: orcid.org/0000-0002-8151-7196,Rongyuan Chen,Guangli Sun,Xialin Liu,Xianchai Lin,Chang He,Liying Xing,Lixian Liu,Lasse D. Jensen,Anil Kumar,Harald F. Langer,Xiangrong Ren,Jianing Zhang,Lijuan Huang,Xiangke Yin,JongKyong Kim  ORCID: orcid.org/0000-0001-7930-723X,Juanhua Zhu,Guanqun Huang,Jiani Li,Weiwei Lu,Wei Chen,Juanxi Liu,Jiaxin Hu,Qihang Sun,Weisi Lu,Lekun Fang  ORCID: orcid.org/0000-0002-0296-292X,Shasha Wang,Haiqing Kuang,Yihan Zhang,Geng Tian,Jia Mi,Bi-Ang Kang,Masashi Narazaki,Aaron Prodeus,Luc Schoonjans,David M. Ornitz  ORCID: orcid.org/0000-0003-1592-7629,Jean Gariepy,Guy Eelen  ORCID: orcid.org/0000-0003-3354-5819,Mieke Dewerchin,Yunlong Yang  ORCID: orcid.org/0000-0003-1551-9828,Jing-Song Ou,Antonio Mora  ORCID: orcid.org/0000-0003-1344-1131,Jin Yao,Chen Zhao,Yizhi Liu,Peter Carmeliet  ORCID: orcid.org/0000-0001-7961-1821,Yihai Cao  ORCID: orcid.org/0000-0003-1308-0065 &…Xuri Li 
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.