Brain pericytes contribute to the induction and up-regulation of blood–brain barrier functions through transforming growth factor-β production
Abstract
The blood-brain barrier (BBB) is a highly organized multicellular complex consisting of an endothelium, brain pericytes and astrocytes. The present study was aimed at evaluating the role of brain pericytes in the induction and maintenance of BBB functions and involvement of transforming growth factor-beta (TGF-beta) in the functional properties of pericytes. We used an in vitro BBB model established by coculturing immortalized mouse brain capillary endothelial (MBEC4) cells with a primary culture of rat brain pericytes. The coculture with rat pericytes significantly decreased the permeability to sodium fluorescein and the accumulation of rhodamine 123 in MBEC4 cells, suggesting that brain pericytes induce and up-regulate the BBB functions. Rat brain pericytes expressed TGF-beta1 mRNA. The pericyte-induced enhancement of BBB functions was significantly inhibited when cells were treated with anti-TGF-beta1 antibody (10 microg/ml) or a TGF-beta type I receptor antagonist (SB431542) (10 microM) for 12 h. In MBEC4 monolayers, a 12 h exposure to TGF-beta1 (1 ng/ml) significantly facilitated the BBB functions, this facilitation being blocked by SB431542. These findings suggest that brain pericytes contribute to the up-regulation of BBB functions through continuous TGF-beta production.
Key Biomarkers
Cited By (4)
- Structural brain abnormalities in patients with inflammatory illness acquired following exposure to water-damaged buildings: a volumetric MRI study using NeuroQuantNeurotoxicology and Teratology · 2014
- Astrocyte-specific hypoxia-inducible factor 1 (HIF-1) does not disrupt the endothelial barrier during hypoxia in vitroFluids and Barriers of the CNS · 2021
- Inhibition of Transforming Growth Factor-β Production in Brain Pericytes Contributes to Cyclosporin A-Induced Dysfunction of the Blood-Brain BarrierCellular and Molecular Neurobiology · 2007
- TGFß1 Stimulates the Over-Production of White Matter Astrocytes from Precursors of the “Brain Marrow” in a Rodent Model of Neonatal EncephalopathyPLoS ONE · 2010
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