Journal
FEBS JOURNAL
Volume 280, Issue 15, Pages 3658-3668Publisher
WILEY
DOI: 10.1111/febs.12359
Keywords
brain microvascular endothelial cells; insulin-like growth factor-1 (IGF-1); ischemia; neuron
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Funding
- National Natural Science Foundation of China [81102679]
- Fundamental Research Funds for the Central public welfare research institutes [ZZ070824]
- National Science & Technology Major Project of China [2009ZX09502-014]
- Ministry of Education
- Key Laboratory of Chinese Internal Medicine
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Insulin-like growth factor (IGF)-1 is essential for the development of the nervous system, and is present in many cell types. Relatively little is known about IGF-1 expression in brain microvascular endothelial cells (BMECs). For invivo studies, we examined the expression of IGF-1 and insulin-like growth factor-binding protein (IGFBP)-2 after focal cerebral ischemia for 12h, 24h, 3days and 7days, utilizing a permanent middle cerebral artery occlusion (MCAO) model in rats. For invitro studies, we examined the levels of IGF-1 and IGFBP-2 in the culture medium or primary culture of BMECs injured by oxygen-glucose deprivation (OGD). Then, we elucidated the protective effects of IGF-1 on cortical neurons injured by OGD and the possible mechanism. In addition, we investigated the effect of BMEC-conditioned medium on IGF-1 receptor expression in neurons. The results showed that IGF-1 expression increased in serum and brain tissue, whereas IGFBP-2 expression decreased in brain tissue of MCAO-injured rats. In primary culture of BMECs, the expression levels of IGF-1 and IGFBP-2 were significantly higher under OGD conditions in culture. IGF-1 administration improved neuron viability upon normoxia or OGD, and upregulated p-Akt expression. This effect was reversed by LY294002, a specific inhibitor of the phosphoinositide 3-kinase-Akt signaling pathway. Furthermore, conditioned medium from OGD-treated BMECs substantially suppressed neuron viability and the expression of IGF-1 receptor simultaneously. These data demonstrate that therapeutic strategies that prioritize the early recovery of the IGF-1 system in BMECs might be promising in ischemic injury.
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