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Chandler (TLC2 from the Heart) Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,3,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>The blood\u2013brain 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\u2212\/\u2212 mice also showed a reduction in laminin protein expression in parenchymal basement membranes. Blood vessels in the Itga7\u2212\/\u2212 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.<\/jats:p>","DOI":"10.1242\/dev.201356","type":"journal-article","created":{"date-parts":[[2023,3,24]],"date-time":"2023-03-24T05:36:59Z","timestamp":1679636219000},"source":"Crossref","is-referenced-by-count":27,"title":["The alpha7 integrin subunit in astrocytes promotes endothelial blood\u2013brain barrier integrity"],"prefix":"10.1242","volume":"150","author":[{"given":"Zhihua","family":"Chen","sequence":"first","affiliation":[{"name":"University of Texas M. D. Anderson Cancer Center 1 Department of Neurosurgery , , Houston, TX 77030 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack R.","family":"Kelly","sequence":"additional","affiliation":[{"name":"University of Texas M. D. 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