Granulocyte colony-stimulating factor stimulates neurogenesis via vascular endothelial growth factor with STAT activation.
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.
Jung
Keun-Hwa
KH
Stroke and Neural Stem Cell Laboratory in Clinical Research Institute, Department of Neurology, Seoul National University Hospital, Seoul, South Korea.
Chu
Kon
K
Lee
Soon-Tae
ST
Kim
Se-Jeong
SJ
Sinn
Dong-In
DI
Kim
Seung U
SU
Kim
Manho
M
Roh
Jae-Kyu
JK
D001921:Brain / Q000166:cytology; D001973:Bromodeoxyuridine; D064026:Calbindins; D002452:Cell Count / Q000379:methods; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004622:Embryo, Mammalian; D042783:Endothelial Cells / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007211:Indoles; D007797:Laminin / Q000378:metabolism; D009474:Neurons / Q000502:physiology*; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000502:physiology; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D050791:STAT Transcription Factors / Q000378:metabolism*; D018709:Statistics, Nonparametric; D013234:Stem Cells / Q000187:drug effects*; D014404:Tubulin / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology / Q000502:physiology*
D064026:Calbindins; D004791:Enzyme Inhibitors; D007211:Indoles; D007797:Laminin; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D064030:S100 Calcium Binding Protein G; D050791:STAT Transcription Factors; D014404:Tubulin; D042461:Vascular Endothelial Growth Factor A; D016179:Granulocyte Colony-Stimulating Factor; C007293:DAPI; D001973:Bromodeoxyuridine