Annexin A2 is a Robo4 ligand that modulates ARF6 activation-associated cerebral trans-endothelial permeability
Autor: | Qiuchen Zhao, Xiaoying Wang, Chongjie Cheng, Wenlu Li, Zhanyang Yu, Haibin Dai, Zhong Chen, Zhigang Chen, Eng H. Lo, Lena Huang, Jing Yuan, Katherine A. Hajjar |
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Rok vydání: | 2018 |
Předmět: |
Receptors
Cell Surface Cell Line Capillary Permeability Mice 03 medical and health sciences 0302 clinical medicine medicine Animals Humans Receptor Annexin A2 Mice Knockout ADP-Ribosylation Factors Chemistry Endothelial Cells Original Articles Human brain Hypoxia (medical) Ligand (biochemistry) Cell Hypoxia Cell biology Endothelial stem cell medicine.anatomical_structure Neurology Membrane protein ADP-Ribosylation Factor 6 Blood-Brain Barrier Knockout mouse Neurology (clinical) medicine.symptom Cardiology and Cardiovascular Medicine 030217 neurology & neurosurgery |
Zdroj: | J Cereb Blood Flow Metab |
ISSN: | 1559-7016 0271-678X |
Popis: | Blood–brain barrier (BBB) disruption in neurological disorders remains an intractable problem with limited therapeutic options. Here, we investigate whether the endothelial cell membrane protein annexin A2 (ANXA2) may play a role in reducing trans-endothelial permeability and maintaining cerebrovascular integrity after injury. Compared with wild-type mice, the expression of cerebral endothelial junctional proteins was reduced in E15.5 and adult ANXA2 knockout mice, along with increased leakage of small molecule tracers. In human brain endothelial cells that were damaged by hypoxia plus IL-1β, treatment with recombinant ANXA2 (rA2) rescued the expression of junctional proteins and decreased trans-endothelial permeability. These protective effects were mediated in part by interactions with F-actin and VE-cadherin, and the ability of rA2 to modulate signaling via the roundabout guidance receptor 4 (Robo4)-paxillin-ADP-ribosylation factor 6 (ARF6) pathway. Taken together, these observations suggest that ANXA2 may be associated with the maintenance of endothelial tightness after cerebrovascular injury. ANXA2-mediated pathways should be further explored as potential therapeutic targets for protecting the BBB in neurological disorders. |
Databáze: | OpenAIRE |
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