TY - JOUR
T1 - Heparin-binding epidermal growth factor-like growth factor
T2 - Hypoxia-inducible expression in vitro and stimulation of neurogenesis in vitro and in vivo
AU - Jin, Kunlin
AU - Ou Mao, Xiao
AU - Sun, Yunjuan
AU - Xie, Lin
AU - Jin, Lan
AU - Nishi, Eiichiro
AU - Klagsbrun, Michael
AU - Greenberg, David A.
PY - 2002/7/1
Y1 - 2002/7/1
N2 - Heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) is found in cerebral neurons, and its expression is increased after hypoxic or ischemic injury, which also stimulates neurogenesis. To investigate the possible role of HB-EGF in hypoxic-ischemic induction of neurogenesis, we measured its expression, effects, and target receptors in embryonic murine cerebral cortical cultures and in adult rat brain. Hypoxia increased HB-EGF expression by ∼50% in cortical cultures, where expression was associated with mature and immature neurons. HB-EGF (5-100 ng/ml) stimulated by ∼80% the incorporation of bromodeoxyuridine (BrdU) into cultured cells that expressed the HB-EGF receptors epidermal growth factor receptor (EGFR)/avian erythroblastic leukemia viral oncogene homolog 1 (ErbB1) and N-arginine dibasic convertase (NRDc). Intracerebroventricular administration of HB-EGF in adult rats increased BrdU labeling in the subventricular zone and in the subgranular zone of dentate gyrus, where EGFR/ErbB1 and NRDc were also expressed and where ischemia-induced neurogenesis is observed. We conclude that HB-EGF stimulates neurogenesis in proliferative zones of the adult brain that are also affected in ischemia and that it does so by interacting with EGFR/ErbB1 and possibly NRDc. Therefore, HB-EGF may help to trigger proliferation of neuronal precursors in brain after hypoxic or ischemic injury.
AB - Heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) is found in cerebral neurons, and its expression is increased after hypoxic or ischemic injury, which also stimulates neurogenesis. To investigate the possible role of HB-EGF in hypoxic-ischemic induction of neurogenesis, we measured its expression, effects, and target receptors in embryonic murine cerebral cortical cultures and in adult rat brain. Hypoxia increased HB-EGF expression by ∼50% in cortical cultures, where expression was associated with mature and immature neurons. HB-EGF (5-100 ng/ml) stimulated by ∼80% the incorporation of bromodeoxyuridine (BrdU) into cultured cells that expressed the HB-EGF receptors epidermal growth factor receptor (EGFR)/avian erythroblastic leukemia viral oncogene homolog 1 (ErbB1) and N-arginine dibasic convertase (NRDc). Intracerebroventricular administration of HB-EGF in adult rats increased BrdU labeling in the subventricular zone and in the subgranular zone of dentate gyrus, where EGFR/ErbB1 and NRDc were also expressed and where ischemia-induced neurogenesis is observed. We conclude that HB-EGF stimulates neurogenesis in proliferative zones of the adult brain that are also affected in ischemia and that it does so by interacting with EGFR/ErbB1 and possibly NRDc. Therefore, HB-EGF may help to trigger proliferation of neuronal precursors in brain after hypoxic or ischemic injury.
KW - Epidermal growth factor receptor (EGFR/ErbB1)
KW - Heparin-binding epidermal growth factor-like growth factor (HB-EGF)
KW - Hypoxia
KW - Ischemia
KW - N-arginine dibasic convertase (NRDc)
KW - Neurogenesis
UR - http://www.scopus.com/inward/record.url?scp=0036662775&partnerID=8YFLogxK
U2 - 10.1523/jneurosci.22-13-05365.2002
DO - 10.1523/jneurosci.22-13-05365.2002
M3 - Article
C2 - 12097488
AN - SCOPUS:0036662775
SN - 0270-6474
VL - 22
SP - 5365
EP - 5373
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 13
ER -