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Granulocyte colony-stimulating factor stimulates neurogenesis via vascular endothelial growth factor with STAT activation.

Authors
Jung, KH; Chu, K; Lee, ST; Kim, SJ; Sinn, DI; Kim, SU; Kim, M; Roh, JK
Citation
Brain research, 1073-1074190-201, 2006
Journal Title
Brain research
ISSN
0006-89931872-6240
Abstract
The adult brain harbors multipotent stem cells, which reside in specialized niches that support self-renewal. Granulocyte colony-stimulating factor (G-CSF) induces bone marrow stem cells proliferation and mobilization from their niche, and activates endothelial cell proliferation, which might help to establish a vascular niche for neural stem cells (NSCs). Here, we show that G-CSF induced receptor-mediated proliferation and differentiation of neural precursors in human NSCs cultures and in adult rat brain in vivo. In human NSCs cultures, G-CSF activated STAT3 and 5, and increased VEGF and its receptor, VEGFR2 (Flk-1) expression, and VEGFR2 tyrosine kinase inhibitor blocked the neurogenesis stimulated by G-CSF. G-CSF also activated endothelial cell proliferation in adult rat brain in vivo. Our results indicate that G-CSF stimulates neurogenesis through reciprocal interaction with VEGF and STAT activation.
MeSH terms
Brain/cytologyBromodeoxyuridine/diagnostic useCalcium-Binding Protein, Vitamin D-Dependent/metabolismCell Count/methodsCell Proliferation/drug effectsCell Survival/drug effectsCell Survival/physiologyCells, CulturedDose-Response Relationship, DrugDrug InteractionsEmbryo, MammalianEndothelial Cells/drug effectsEnzyme Activation/drug effectsEnzyme Inhibitors/pharmacologyEnzyme-Linked Immunosorbent Assay/methodsGranulocyte Colony-Stimulating Factor/pharmacology*HumansImmunohistochemistry/methodsIndoles/diagnostic useLaminin/metabolismNeurons/physiology*Receptors, Granulocyte Colony-Stimulating Factor/physiologySTAT Transcription Factors/metabolism*Statistics, NonparametricStem Cells/drug effects*Tubulin/metabolismVascular Endothelial Growth Factor A/pharmacologyVascular Endothelial Growth Factor A/physiology*
DOI
10.1016/j.brainres.2005.12.037
PMID
16423324
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Neurology
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