TY  - JOUR
AU  - Schumacher, Leonie
AU  - Slimani, Rédouane
AU  - Zizmare, Laimdota
AU  - Ehlers, Jakob
AU  - Kleine Borgmann, Felix
AU  - Fitzgerald, Julia C
AU  - Fallier-Becker, Petra
AU  - Beckmann, Anja
AU  - Grißmer, Alexander
AU  - Meier, Carola
AU  - El-Ayoubi, Ali
AU  - Devraj, Kavi
AU  - Mittelbronn, Michel
AU  - Trautwein, Christoph
AU  - Naumann, Ulrike
TI  - TGF-Beta Modulates the Integrity of the Blood Brain Barrier In Vitro, and Is Associated with Metabolic Alterations in Pericytes.
JO  - Biomedicines
VL  - 11
IS  - 1
SN  - 2227-9059
CY  - Basel
PB  - MDPI
M1  - DKFZ-2023-00142
SP  - 214
PY  - 2023
AB  - 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.
KW  - blood–brain barrier (Other)
KW  - glioblastoma (Other)
KW  - metabolomics (Other)
KW  - transforming growth factor beta (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:36672722
C2  - pmc:PMC9855966
DO  - DOI:10.3390/biomedicines11010214
UR  - https://inrepo02.dkfz.de/record/212423
ER  -