Axin1 participates in blood-brain barrier protection during experimental ischemic stroke via phosphorylation at Thr485 in rats.

Yugang Wang, Yi Zhong, Xiang Xu, Xiang Li, Haiying Li, Haitao Shen, Wenjie Wang, Qi Fang

Journal of chemical neuroanatomy 2023 Jan

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Axin1 takes an important part in a variety of signaling pathway, such as MEKK1, GSK3β, and β-catenin, and plays a variety of physiological functions; but its effects on the brain-blood barrier (BBB) and stroke remain unclear. To explore the effects and underlying mechanisms of Axin1 on the BBB in ischemic stroke, Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO). Human brain microvascular endothelial cells (HBMEC) were subjected to oxygen/glucose deprivation/reoxygenation (OGD/R) to imitate ischemia/reperfusion (I/R) injury. We found that Axin1 was upregulated in HBMEC after OGD without reoxygenation, and downregulated in the injured hemisphere after MCAO without reperfusion. Tight junction (TJ) proteins were upregulated both in HBMEC after OGD without reoxygenation and in ischemic penumbra of the injured hemisphere in rats after MCAO without reperfusion. TJ proteins were downregulated after MCAO/R in rats. Overexpression of Axin1 upregulated the levels of TJ proteins, which alleviated BBB permeability, reduced infarction volume, and ultimately improved neurological behavioral indicators after I/R injury. Furthermore, inhibiting phosphorylation of Axin1 at Thr485 notably increased the expression of Snail and decreased the expression of TJ proteins. Our findings demonstrate that Axin1 participates in BBB protection and improvement of neurological functions during ischemic stroke by regulating TJ proteins. Axin1 may serve as a potential novel candidate to protect BBB and relieve brain injury. Copyright © 2022 Elsevier B.V. All rights reserved.

Citation

Yugang Wang, Yi Zhong, Xiang Xu, Xiang Li, Haiying Li, Haitao Shen, Wenjie Wang, Qi Fang. Axin1 participates in blood-brain barrier protection during experimental ischemic stroke via phosphorylation at Thr485 in rats. Journal of chemical neuroanatomy. 2023 Jan;127:102204