VEGF-B prevents excessive angiogenesis by inhibiting FGF2/FGFR1 pathway

Medientyp: E-Artikel

Titel: VEGF-B prevents excessive angiogenesis by inhibiting FGF2/FGFR1 pathway

Beteiligte: Lee, Chunsik [Verfasser:in]; Chen, Rongyuan [Verfasser:in]; Sun, Guangli [Verfasser:in]; Liu, Xialin [Verfasser:in]; Lin, Xianchai [Verfasser:in]; He, Chang [Verfasser:in]; Xing, Liying [Verfasser:in]; Liu, Lixian [Verfasser:in]; Jensen, Lasse D. [Verfasser:in]; Kumar, Anil [Verfasser:in]; Langer, Harald [Verfasser:in]; Ren, Xiangrong [Verfasser:in]; Zhang, Jianing [Verfasser:in]; Huang, Lijuan [Verfasser:in]; Yin, Xiangke [Verfasser:in]; Kim, JongKyong [Verfasser:in]; Zhu, Juanhua [Verfasser:in]; Huang, Guanqun [Verfasser:in]; Li, Jiani [Verfasser:in]; Lu, Weiwei [Verfasser:in]; Chen, Wei [Verfasser:in]; Liu, Juanxi [Verfasser:in]; Hu, Jiaxin [Verfasser:in]; Sun, Qihang [Verfasser:in]; Lu, Weisi [Verfasser:in]; Fang, Lekun [Verfasser:in]; Wang, Shasha [Verfasser:in]; Kuang, Haiqing [Verfasser:in]; Zhang, Yihan [Verfasser:in]; Tian, Geng [Verfasser:in]; Mi, Jia [Verfasser:in]; Kang, Bi-Ang [Verfasser:in]; Narazaki, Masashi [Verfasser:in]; Prodeus, Aaron [Verfasser:in]; Schoonjans, Luc [Verfasser:in]; Ornitz, David M. [Verfasser:in]; Gariepy, Jean [Verfasser:in]; Eelen, Guy [Verfasser:in]; Dewerchin, Mieke [Verfasser:in]; Yang, Yunlong [Verfasser:in]; Ou, Jing-Song [Verfasser:in]; Mora, Antonio [Verfasser:in]; Yao, Jin [Verfasser:in]; Zhao, Chen [Verfasser:in]; Liu, Yizhi [Verfasser:in]; Carmeliet, Peter [Verfasser:in]; Cao, Yihai [Verfasser:in]; Li, Xuri [Verfasser:in]

Erschienen: 18 August 2023

Sprache: Englisch

DOI: 10.1038/s41392-023-01539-9

Identifikator:

Schlagwörter: Cell biology ; Molecular biology

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Beschreibung: 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.

Zugangsstatus: Freier Zugang

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