Astrocytic laminin regulates pericyte differentiation and maintains blood-brain barrier integrity

Here they show that lack of astrocytic laminin, a brain-specific BM component, induces BBB breakdown. Use conditional knockout mice and an acute adenovirus-mediated knockdown model. Using functional blocking antibody and RNAi, we further demonstrate that astrocytic laminin, by binding to integrin a2 receptor, prevents pericyte differentiation from the BBB-stabilizing resting stage to the BBB-disrupting contractile stage, and thus maintains the integrity of BBB. Loss of astrocytic laminin also decreases aquaporin-4 (AQP4) and tight junction protein expression. These results indicate that astrocytic laminin maintains the integrity of BBB through, at least in part, regulation of pericyte differentiation.