Endothelial cell activation by interleukin-1 and extracellular matrix laminin-10 occurs via the YAP signalling pathway.

ABSTRACT

Laminin-10 (LM-10) is a key regulator of blood-brain barrier (BBB) repair after hypoxia and inflammation. Here we investigated the signalling mechanisms regulated by LM-10 in human brain endothelial cell line hCMEC/D3 in response to interleukin(IL)-1beta(ß) in vitro. LM-10 promoted endothelial proliferation and repair of an endothelial monolayer after scratch injury, and upregulated IL-1ß-induced ICAM-1 and VCAM-1 expression. IL-1ß and LM-10 regulated YAP signalling pathway in endothelial cells leading to differential expression of YAP target genes, ctgf and serpine-1, providing evidence that the YAP signalling pathway could be a new therapeutic target for the treatment of BBB dysfunction in CNS diseases.