The alpha7 Integrin Subunit in Astrocytes Promotes Endothelial Blood-Brain Barrier Integrity

Authors

Zhihua Chen
Jack R Kelly
John E Morales
Raymond C Sun
Arpan De
Dean J Burkin
Joseph H McCarty

Language

English

Publication Date

3-15-2023

Journal

Angiogenesis

DOI

10.1007/s10456-025-10019-3

PMID

41353666

PMCID

PMC12682726

PubMedCentral® Posted Date

12-7-2025

PubMedCentral® Full Text Version

Post-print

Abstract

The blood-brain barrier (BBB) is a vascular endothelial cell boundary that partitions the circulation from the central nervous system to promote normal brain health. We have a limited understanding of how the BBB is formed during development and maintained in adulthood. We used quantitative transcriptional profiling to investigate whether specific adhesion molecules are involved in BBB functions, with an emphasis on understanding how astrocytes interact with endothelial cells. Our results reveal a striking enrichment of multiple genes encoding laminin subunits as well as the laminin receptor gene Itga7, which encodes the alpha7 integrin subunit, in astrocytes. Genetic ablation of Itga7 in mice led to aberrant BBB permeability and progressive neurological pathologies. Itga7-/- mice also showed a reduction in laminin protein expression in parenchymal basement membranes. Blood vessels in the Itga7-/- brain showed separation from surrounding astrocytes and had reduced expression of the tight junction proteins claudin 5 and ZO-1. We propose that the alpha7 integrin subunit in astrocytes via adhesion to laminins promotes endothelial cell junction integrity, all of which is required to properly form and maintain a functional BBB.

Keywords

Mice, Animals, Blood-Brain Barrier, Astrocytes, Laminin, Endothelial Cells, Integrins, Tight Junctions, Angiogenesis, Itgb8, β8 integrin, Single-cell RNA, Spatial transcriptomics, Neurovascular unit, Blood-brain barrier, Extracellular matrix, Cell adhesion

Published Open-Access

yes

Recommended Citation

Chen, Zhihua; Kelly, Jack R; Morales, John E; et al., "The alpha7 Integrin Subunit in Astrocytes Promotes Endothelial Blood-Brain Barrier Integrity" (2023). Faculty, Staff and Student Publications. 6257.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/6257