Perinatal hypoxia-ischemia decreased neuronal but increased cerebral vascular endothelial IGFBP3 expression.
In adults, insulin-like growth factor binding protein 3 (IGFBP3) is the main carrier protein for circulating insulin-like growth factors (IGFs) (IGF-I and -II). While most IGFBP3 is synthesized in the liver, it is also expressed locally by many cell types including vascular endothelial cells. The regulation of this endothelial IGFBP3 expression, especially in response to hypoxic-ischemic injury, has not been investigated in vivo. Using in situ hybridization histochemistry, we studied the cellular distribution of IGFBP3 mRNA in rat brains following hypoxic-ischemic injury at 1, 5, 24, and 72 h of recovery. In normal P7 rat brain, IGFBP3 mRNA was found in neurons within the thalamus, hippocampus, and amygdaloid. Low levels of IGFBP3 mRNA were also detected in cerebral vascular endothelial cells. After the hypoxic-ischemic injury, the levels of neuronal IGFBP3 mRNA substantially decreased within 24 h in areas that were normally supplied by the middle cerebral artery. In the meantime, there was an immediate increase in IGFBP3 expression in vascular endothelial cells throughout the affected hemisphere. This vascular IGFBP3 expression was further enhanced with the highest level at 24 h of recovery whereas neuronal IGFBP3 expression was further decreased. By 72 h of recovery, IGFBP3 was no longer expressed in vascular endothelial cells. Taken together, the activation of IGFBP3 is a likely mechanism by which vascular endothelial cells respond to hypoxic-ischemic insult. In addition, increased endothelial IGFBP3 may modulate the interaction of IGFs with IGF-I receptors at the site of injury and/or act independently on endothelial cell growth.
Lee
W H
WH
Department of Pediatrics, Indiana University School of Medicine, Indianapolis 46202-5119, USA. wlee@iupui.edu
Wang
G M
GM
Yang
X L
XL
Seaman
L B
LB
Vannucci
S I
SI
D000818:Animals; D001921:Brain / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D013002:Somatomedins
D018972:Insulin-Like Growth Factor Binding Protein 3; D012333:RNA, Messenger; D013002:Somatomedins