期刊
NATURE
卷 545, 期 7653, 页码 224-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nature22322
关键词
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资金
- American Heart Association [15POST25830021]
- Brown-Coxe Fellowship from Yale University
- Research Foundation Flanders (FWO)
- Flemish Government [IUAP P7/03]
- FWO [G.0598.12, G.0532.10, G.0817.11, G.0834.13, 1.5.202.10.]
- Leducq Transatlantic Network ARTEMIS
- AXA Research Fund [1465]
- Foundation against Cancer
- European Research Council (ERC) Advanced Research Grant [EU-ERC269073]
- Max Planck Society
- ERC Starting Grant ANGIOMET [311546]
- Deutsche Forschungsgemeinschaft [SFB 834]
- Excellence Cluster Cardiopulmonary System [EXC 147/1]
- LOEWE grant Ub-Net
- DZHK (German Center for Cardiovascular Research)
- European Molecular Biology Organization Young Investigator Programme
- National Institutes of Health [HL053793, HL084619]
- ARTEMIS Leducq Transatlantic Network
- European Research Council (ERC) [311546] Funding Source: European Research Council (ERC)
Blood and lymphatic vasculatures are intimately involved in tissue oxygenation and fluid homeostasis maintenance. Assembly of these vascular networks involves sprouting, migration and proliferation of endothelial cells. Recent studies have suggested that changes in cellular metabolism are important to these processes(1). Although much is known about vascular endothelial growth factor (VEGF)-dependent regulation of vascular development and metabolism(2,3), little is understood about the role of fibroblast growth factors (FGFs) in this context(4). Here we identify FGF receptor (FGFR) signalling as a critical regulator of vascular development. This is achieved by FGF-dependent control of c-MYC (MYC) expression that, in turn, regulates expression of the glycolytic enzyme hexokinase 2 (HK2). A decrease in HK2 levels in the absence of FGF signalling inputs results in decreased glycolysis, leading to impaired endothelial cell proliferation and migration. Pan-endothelial-and lymphatic-specific Hk2 knockouts phenocopy blood and/or lymphatic vascular defects seen in Fgfr1/Fgfr3 double mutant mice, while HK2 overexpression partly rescues the defects caused by suppression of FGF signalling. Thus, FGF-dependent regulation of endothelial glycolysis is a pivotal process in developmental and adult vascular growth and development.
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