The role of pericytic laminin in blood brain barrier integrity maintenance.
Laminin, a major component of the basement membrane, plays an important role in blood brain barrier regulation. At the neurovascular unit, brain endothelial cells, astrocytes, and pericytes synthesize and deposit different laminin isoforms into the basement membrane. It has been shown that laminin α4 (endothelial laminin) regulates vascular integrity at embryonic/neonatal stage, while astrocytic laminin maintains vascular integrity in adulthood. Here, we investigate the function of pericyte-derived laminin in vascular integrity. Using a conditional knockout mouse line, we report that loss of pericytic laminin leads to hydrocephalus and BBB breakdown in a small percentage (10.7%) of the mutants. Interestingly, BBB disruption always goes hand-in-hand with hydrocephalus in these mutants, and neither symptom is observed in the rest 89.3% of the mutants. Further mechanistic studies show that reduced tight junction proteins, diminished AQP4 expression, and decreased pericyte coverage are responsible for the BBB disruption. Together, these data suggest that pericyte-derived laminin is involved in the maintenance of BBB integrity and regulation of ventricular size/development.
College of Pharmacy, University of Minnesota, 1110 Kirby Drive, Duluth, MN, 55812, USA.
Jyoti
J
Gautam
College of Pharmacy, University of Minnesota, 1110 Kirby Drive, Duluth, MN, 55812, USA.
Xuanming
X
Zhang
College of Pharmacy, University of Minnesota, 1110 Kirby Drive, Duluth, MN, 55812, USA.
Yao
Y
Yao
D000818:Animals; D051401:Aquaporin 4 / Q000378:metabolism; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D003893:Desmin / Q000378:metabolism; D006849:Hydrocephalus / Q000378:metabolism / Q000473:pathology; D007797:Laminin / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D020286:Pericytes / Q000166:cytology / Q000378:metabolism; D010641:Phenotype; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics / Q000378:metabolism; D062725:Tight Junction Proteins / Q000378:metabolism
C496031:Aqp4 protein, mouse; D051401:Aquaporin 4; D003893:Desmin; D007797:Laminin; D062725:Tight Junction Proteins; D020797:Receptor, Platelet-Derived Growth Factor beta