Hypoxia-induced blood-brain barrier dysfunction is prevented by pericyte-conditioned media via attenuated actomyosin contractility and claudin-5 stabilization.

Autor:	Jamieson JJ; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland, USA.; Institute for Nanobiotechnology, Johns Hopkins University, Baltimore, Maryland, USA., Lin Y; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland, USA.; Institute for Nanobiotechnology, Johns Hopkins University, Baltimore, Maryland, USA., Malloy N; Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA., Soto D; Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA., Searson PC; Institute for Nanobiotechnology, Johns Hopkins University, Baltimore, Maryland, USA.; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland, USA.; Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, Maryland, USA., Gerecht S; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland, USA.; Institute for Nanobiotechnology, Johns Hopkins University, Baltimore, Maryland, USA.; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland, USA.; Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, Maryland, USA.; Department of Biomedical Engineering, Duke University, Duke, North Carolina, USA.
Jazyk:	angličtina
Zdroj:	FASEB journal : official publication of the Federation of American Societies for Experimental Biology [FASEB J] 2022 May; Vol. 36 (5), pp. e22331.
DOI:	10.1096/fj.202200010RR
Abstrakt:	The blood-brain barrier (BBB) regulates molecular and cellular entry from the cerebrovasculature into the surrounding brain parenchyma. Many diseases of the brain are associated with dysfunction of the BBB, where hypoxia is a common stressor. However, the contribution of hypoxia to BBB dysfunction is challenging to study due to the complexity of the brain microenvironment. In this study, we used a BBB model with brain microvascular endothelial cells and pericytes differentiated from iPSCs to investigate the effect of hypoxia on barrier function. We found that hypoxia-induced barrier dysfunction is dependent upon increased actomyosin contractility and is associated with increased fibronectin fibrillogenesis. We propose a role for actomyosin contractility in mediating hypoxia-induced barrier dysfunction through modulation of junctional claudin-5. Our findings suggest pericytes may protect brain microvascular endothelial cells from hypoxic stresses and that pericyte-derived factors could be candidates for treatment of pathological barrier-forming tissues. (© 2022 Federation of American Societies for Experimental Biology.)
Databáze:	MEDLINE
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