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Publication : Annexin A2 is a Robo4 ligand that modulates ARF6 activation-associated cerebral trans-endothelial permeability.

First Author  Li W Year  2019
Journal  J Cereb Blood Flow Metab Volume  39
Issue  10 Pages  2048-2060
PubMed ID  29786451 Mgi Jnum  J:318501
Mgi Id  MGI:6859911 Doi  10.1177/0271678X18777916
Citation  Li W, et al. (2019) Annexin A2 is a Robo4 ligand that modulates ARF6 activation-associated cerebral trans-endothelial permeability. J Cereb Blood Flow Metab 39(10):2048-2060
abstractText  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-1beta, 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.
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