title: Astrocytic laminin regulates pericyte differentiation and maintains blood brain barrier integrity.
abstract: Blood brain barrier (BBB) breakdown is not only a consequence of but also contributes to many neurological disorders, including stroke and Alzheimer's disease. How the basement membrane (BM) contributes to the normal functioning of the BBB remains elusive. Here we use conditional knockout mice and an acute adenovirus-mediated knockdown model to show that lack of astrocytic laminin, a brain-specific BM component, induces BBB breakdown. Using functional blocking antibody and RNAi, we further demonstrate that astrocytic laminin, by binding to integrin α2 receptor, prevents pericyte differentiation from the BBB-stabilizing resting stage to the BBB-disrupting contractile stage, and thus maintains the integrity of BBB. Additionally, loss of astrocytic laminin decreases aquaporin-4 (AQP4) and tight junction protein expression. Altogether, we report a critical role for astrocytic laminin in BBB regulation and pericyte differentiation. These results indicate that astrocytic laminin maintains the integrity of BBB through, at least in part, regulation of pericyte differentiation.
authors.affiliation: Laboratory of Neurobiology and Genetics, The Rockefeller University, 1230 York Avenue, New York, New York 10065, USA.
authors.forename: Yao
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Laboratory of Neurobiology and Genetics, The Rockefeller University, 1230 York Avenue, New York, New York 10065, USA.
authors.forename: Zu-Lin
authors.initials: ZL
authors.lastname: Chen
authors.affiliation: Laboratory of Neurobiology and Genetics, The Rockefeller University, 1230 York Avenue, New York, New York 10065, USA.
authors.forename: Erin H
authors.initials: EH
authors.lastname: Norris
authors.affiliation: Laboratory of Neurobiology and Genetics, The Rockefeller University, 1230 York Avenue, New York, New York 10065, USA.
authors.forename: Sidney
authors.initials: S
authors.lastname: Strickland
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology* / Q000378:metabolism*; D001485:Basement Membrane / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000166:cytology / Q000378:metabolism*; D015153:Blotting, Western; D002478:Cells, Cultured; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007797:Laminin / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D020286:Pericytes / Q000166:cytology / Q000378:metabolism
chemical_list: D007797:Laminin