Please use this identifier to cite or link to this item: doi:10.22028/D291-38786
Title: TGF-Beta Modulates the Integrity of the Blood Brain Barrier In Vitro, and Is Associated with Metabolic Alterations in Pericytes
Author(s): Schumacher, Leonie
Slimani, Rédouane
Zizmare, Laimdota
Ehlers, Jakob
Kleine Borgmann, Felix
Fitzgerald, Julia C.
Fallier-Becker, Petra
Beckmann, Anja
Grißmer, Alexander
Meier, Carola
El-Ayoubi, Ali
Devraj, Kavi
Mittelbronn, Michel
Trautwein, Christoph
Naumann, Ulrike
Language: English
Title: Biomedicines
Volume: 11
Issue: 1
Publisher/Platform: MDPI
Year of Publication: 2023
Free key words: glioblastoma
blood–brain barrier
transforming growth factor beta
DDC notations: 610 Medicine and health
Publikation type: Journal Article
Abstract: The blood–brain barrier (BBB) is a selectively permeable boundary that separates the circulating blood from the extracellular fluid of the brain and is an essential component for brain homeostasis. In glioblastoma (GBM), the BBB of peritumoral vessels is often disrupted. Pericytes, being important to maintaining BBB integrity, can be functionally modified by GBM cells which induce proliferation and cell motility via the TGF-β-mediated induction of central epithelial to mesenchymal transition (EMT) factors. We demonstrate that pericytes strengthen the integrity of the BBB in primary endothelial cell/pericyte co-cultures as an in vitro BBB model, using TEER measurement of the barrier integrity. In contrast, this effect was abrogated by TGF-β or conditioned medium from TGF-β secreting GBM cells, leading to the disruption of a so far intact and tight BBB. TGF-β notably changed the metabolic behavior of pericytes, by shutting down the TCA cycle, driving energy generation from oxidative phosphorylation towards glycolysis, and by modulating pathways that are necessary for the biosynthesis of molecules used for proliferation and cell division. Combined metabolomic and transcriptomic analyses further underscored that the observed functional and metabolic changes of TGF-β-treated pericytes are closely connected with their role as important supporting cells during angiogenic processes.
DOI of the first publication: 10.3390/biomedicines11010214
URL of the first publication:
Link to this record: urn:nbn:de:bsz:291--ds-387867
ISSN: 2227-9059
Date of registration: 23-Jan-2023
Description of the related object: Supplementary Materials
Related object:
Faculty: M - Medizinische Fakultät
Department: M - Anatomie und Zellbiologie
Professorship: M - Prof. Dr. Carola Meier
Collections:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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