Astrocytic laminin regulates pericyte differentiation and maintains blood brain barrier integrity
Open accessAbstract
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.
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Conditional deletion of astrocytic laminin γ1 and acute knockdown of laminin α2 lead to breakdown of the basement membrane, loss of astrocyte endfeet polarity, reduced blood-brain barrier tight junction expression, and blood-brain barrier disruption.
“Conditional deletion of astrocytic laminin 𝛄 1 and acute knockdown of laminin 𝛂 2 lead to breakdown of the basement membrane, loss of astrocyte endfeet polarity, reduced BBB TJs expression, and BBB disruption (667).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [667]
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Experimental — accuracy not yet measuredAstrocytes influence blood-brain barrier integrity, and transporters at astrocytic endfeet are relevant to the blood-brain barrier because astrocytic endfeet surround brain vessels.
“While astrocytes also influence BBB integrity and transporters at astrocytic endfeet are relevant to the BBB since astrocytic endfeet surround brain vessels (13, 667, 682), currently the transcriptome or proteome specifically enriched only in astrocytic endfeet has not been examined.”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [667]
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References 62 · Cited by 357
- Authors
- Yao, Y., Chen, Z.-L., Norris, E. H., & Strickland, S.
- Affiliations
- Rockefeller University (US)
- Corresponding author
- Strickland, Sidney
- Venue
- Nature Communications
- Published
- 2014-03-03
- Volume
- 5
- Issue
- 1
- Pages
- 3413-3413
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC3992931
- OpenAlex
- W2020543532
- Cited by
- 357
- References
- 62
- Citations by year
- 2026: 20 · 2025: 34 · 2024: 30 · 2023: 31 · 2022: 49 · 2021: 39 · 2020: 40 · 2019: 26 · 2018: 25 · 2017: 26 · 2016: 19 · 2015: 13 · 2014: 5
- FWCI
- 10.94
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Nature Communications (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Institutes of Health
- Weill Cornell Medical College
- National Institute of Neurological Disorders and Stroke (R01NS050537, NS050537)
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Keywords
- blood-brain barrier integrity, pericyte differentiation, basement membrane, aquaporin-4, tight junction proteins, blood-brain barrier disruption, stroke, Alzheimer's disease
- MeSH terms
- Animals, Astrocytes, Basement Membrane, Blood-Brain Barrier, Cells, Cultured, Humans, Immunohistochemistry, Laminin, Muscle, Smooth, Vascular, Blotting, Western, Mice, Knockout, Pericytes, In Situ Nick-End Labeling, Myocytes, Smooth Muscle, Mice
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