| First Author | Gerber HP | Year | 2002 |
| Journal | Nature | Volume | 417 |
| Issue | 6892 | Pages | 954-8 |
| PubMed ID | 12087404 | Mgi Jnum | J:77388 |
| Mgi Id | MGI:2181517 | Doi | 10.1038/nature00821 |
| Citation | Gerber HP, et al. (2002) VEGF regulates haematopoietic stem cell survival by an internal autocrine loop mechanism. Nature 417(6892):954-8 |
| abstractText | 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. |
