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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 

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VEGF regulates haematopoietic stem cell survival by an internal autocrine loop mechanism.

Vascular endothelial growth factor (VEGF) is a principal regulator of blood vessel formation and haematopoiesis, but the mechanisms by which VEGF differentially regulates these processes have been elusive. Here we describe a regulatory loop by which VEGF controls survival of haematopoietic stem cells (HSCs). We observed a reduction in survival, colony formation and in vivo repopulation rates of HSCs after ablation of the VEGF gene in mice. Intracellularly acting small-molecule inhibitors of VEGF receptor ( VEGFR) tyrosine kinase dramatically reduced colony formation of HSCs, thus mimicking deletion of the VEGF gene. However, blocking VEGF by administering a soluble VEGFR-1, which acts extracellularly, induced only minor effects. These findings support the involvement in HSC survival of a VEGF-dependent internal autocrine loop mechanism (that is, the mechanism is resistant to inhibitors that fail to penetrate the intracellular compartment). Not only ligands selective for VEGF and VEGFR-2 but also VEGFR-1 agonists rescued survival and repopulation of VEGF-deficient HSCs, revealing a function for VEGFR-1 signalling during haematopoiesis.[1]

References

  1. VEGF regulates haematopoietic stem cell survival by an internal autocrine loop mechanism. Gerber, H.P., Malik, A.K., Solar, G.P., Sherman, D., Liang, X.H., Meng, G., Hong, K., Marsters, J.C., Ferrara, N. Nature (2002) [Pubmed]
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