KMID : 0620920180500090117
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Experimental & Molecular Medicine 2018 Volume.50 No. 9 p.117 ~ p.117
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Integrin ¥á5¥â1-Ang1/Tie2 receptor cross-talk regulates brain endothelial cell responses following cerebral ischemia
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Pang Defang
Wang Lu Dong Jing Lai Xiaoyin Huang Qijuan Milner Richard Li Longxuan
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Abstract
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We have previously demonstrated that in response to cerebral ischemia (CI), the growth factor angiopoietin-1 (Ang1) and ¥á5¥â1 integrin are both induced in cerebral vessels, which likely provide positive signals driving the endogenous angiogenic response and vascular protection after CI. However, the precise relationship between endothelial Ang1 and ¥á5¥â1 integrin after CI remains poorly understood. Here, we investigated the effects of the interaction between the Ang1/Tie2 system and ¥á5¥â1 integrin on brain endothelial cells (BECs) under cerebral ischemic conditions in vivo and in vitro. Immunofluorescence analysis demonstrated that integrin ¥á5¥â1 co-localized with Tie2/phosphorylated Tie2 on cerebral vessels in the penumbra. The in vitro study showed that oxygen?glucose deprivation/restoration (OGD/R) induced the expression of the Ang1 receptor Tie2 on BECs in a manner similar to that for integrin ¥á5 and Ang1 in response to OGD/R, accompanied by increased activation of Tie2 and its downstream effectors focal adhesion kinase (FAK) and Akt. Knockdown of ¥á5 integrin markedly suppressed OGD/R-induced Tie2 receptor activation in BECs, while in contrast, priming BECs with Ang1 promoted the expression of ¥á5 integrin as well as the Tie2 downstream transcription factor Ets-1 in OGD-treated BECs. In line with this, Ets-1 knockdown significantly attenuated Ang1-mediated upregulation of ¥á5 integrin. Functionally, Ang1 induced cell migration and tube formation of BECs after OGD, but this effect was inhibited by diminishment of the levels of ¥á5 integrin in BECs. Taken together, our data indicate that the Ang1/Tie2 system cross-talks with integrin ¥á5¥â1 in BECs after CI, which may contribute to the endogenous angiogenic vascular protective response following CI.
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KEYWORD
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Regeneration and repair in the nervous system, Stroke
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