Upregulation of Flk-1 by bFGF via the ERK pathway is essential for VEGF-mediated promotion of neural stem cell proliferation.

Abstract:

:Neural stem cells (NSCs) constitute the cellular basis for embryonic brain development and neurogenesis. The process is regulated by NSC niche including neighbor cells such as vascular and glial cells. Since both vascular and glial cells secrete vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), we assessed the effect of VEGF and bFGF on NSC proliferation using nearly homogeneous NSCs that were differentiated from mouse embryonic stem cells. VEGF alone did not have any significant effect. When bFGF was added, however, VEGF stimulated NSC proliferation in a dose-dependent manner, and this stimulation was inhibited by ZM323881, a VEGF receptor (Flk-1)-specific inhibitor. Interestingly, ZM323881 also inhibited cell proliferation in the absence of exogenous VEGF, suggesting that VEGF autocrine plays a role in the proliferation of NSCs. The stimulatory effect of VEGF on NSC proliferation depends on bFGF, which is likely due to the fact that expression of Flk-1 was upregulated by bFGF via phosphorylation of ERK1/2. Collectively, this study may provide insight into the mechanisms by which microenvironmental niche signals regulate NSCs.

journal_name

Cell Res

journal_title

Cell research

authors

Xiao Z,Kong Y,Yang S,Li M,Wen J,Li L

doi

10.1038/sj.cr.7310126

subject

Has Abstract

pub_date

2007-01-01 00:00:00

pages

73-9

issue

1

eissn

1001-0602

issn

1748-7838

pii

7310126

journal_volume

17

pub_type

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