High-mannose-type glycan of basigin in endothelial cells is essential for the opening of blood-brain barrier induced by hypoxia, cyclophilin A or TNF- α

Am J Pathol. 2023 Nov 29:S0002-9440(23)00446-7. doi: 10.1016/j.ajpath.2023.11.007. Online ahead of print.ABSTRACTPathological opening of blood-brain barrier accelerates the progression of various neural diseases. As an essential molecule for the opening of blood-brain barrier, we have specified basigin, a highly glycosylated transmembrane molecule, in barrier-forming endothelial cells. Here, we analyzed the involvement of basigin in the regulation of blood-brain barrier focusing on its glycosylation forms. First, basigin was found to be expressed as the cell surface molecules with complex-type glycan as well as those with high mannose-type glycan in barrier-forming endothelial cells. Then, monolayers of endothelial cells with suppressed expression of basigin with high-mannose-type glycan was prepared and exposed to pathological stimuli. These monolayers retained their barrier-forming properties even in the presence of pathological stimuli, although their expression of basigin with complex-type glycan was maintained. Also in vivo, the blood-brain barrier in mice which were pretreated intravenously with endoglycosidase H was protected from the opening under pathological stimuli. Furthermore, the pathologically opened blood-brain barrier in streptozotocin-injected mice was successfully closed by intravenous injection of endoglycosidase H. These results demonstrate that high mannose-type glycan of basigin molecule is essential for the opening of blood-brain barrier and therefore ...

Source: Am J Pathol - December 1, 2023 Category: Pathology Authors: Dan Cui Kazuo Yamamoto Eiji Ikeda Source Type: research