Premium
Vascular endothelial growth factor promotes proliferation of cortical neuron precursors by regulating E2F expression
Author(s) -
Yonghua Zhu,
Kunlin Jin,
Ou Mao Xiao,
Greenberg David A.
Publication year - 2003
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.02-0515com
Subject(s) - wortmannin , microbiology and biotechnology , neurogenesis , biology , e2f , vascular endothelial growth factor , kinase , cell growth , cell cycle , pi3k/akt/mtor pathway , cancer research , signal transduction , cell , biochemistry , vegf receptors
Neurogenesis, or the production of new neurons, is regulated by physiological and pathological processes including aging, stress, and brain injury. Many mitogenic and trophic factors that regulate proliferation of nonneuronal cells are also involved in neurogenesis. These include vascular endothelial cell growth factor (VEGF), which stimulates the incorporation of bromodeoxyuridine (BrdU) into neuronal precursor cells in vitro and in the adult rat brain in vivo. Using BrdU labeling as an index of cell proliferation, we found that the in vitro neuroproliferative effect of VEGF was associated with up‐regulation of E2F family transcription factors, cyclin D1, cyclin E, and cdc25. VEGF also increased nuclear expression of E2F1, E2F2, and E2F3, consistent with regulation of the G 1 /S phase transition of the cell cycle. The proliferative effect of VEGF was inhibited by the extracellular signal‐regulated kinase kinase (MEK) inhibitor PD98059, the phospholipase C (PLC) inhibitor U73122, the protein kinase C (PKC) inhibitor GF102390X, and the phosphatidylinositol 3‐kinase (PI3K) inhibitor wortmannin, indicating involvement of multiple signaling pathways. These findings help to provide a molecular basis for some of the recently identified neuronal effects of VEGF. Zhu, Y., Jin, K., Mao, X. O., Greenberg D. A. Vascular endothelial growth factor promotes proliferation of cortical neuron precursors by regulating E2F expression. FASEB J . 17, 186–193 (2003)