Concentration-dependent duality of bFGF in regulation of barrier properties of human brain endothelial cells.
J Cell Physiol
; 236(11): 7642-7654, 2021 11.
Article
en En
| MEDLINE
| ID: mdl-33959949
ABSTRACT
Multiple paracrine factors regulate the barrier properties of human brain capillary endothelial cells (BCECs). Understanding the precise mode of action of these factors remains a challenging task, because of the limited availability of functionally competent BCECs and the use of serum-containing medium. In the present study, we employed a defined protocol for producing BCECs from human inducible pluripotent stem cells. We found that autocrine secretion of basic fibroblast growth factor (bFGF) is necessary for the establishment a tight BCECs barrier, as revealed by measurements of transendothelial electric resistance (TEER). In contrast, addition of exogenous bFGF in concentrations higher than 4 ng/ml inhibited TEER in a concentration-dependent manner. Exogenous bFGF did not significantly affect expression and distribution of tight junction proteinsâclaudin-5, occludin and zonula occludens (ZO)-1. Treatment with FGF receptor blocker PD173074 (15 µM) suppressed inhibitory effects of bFGF and induced nuclear translocation of protein ZO-1. Inhibition of phosphoinositide 3-Kinase (PI-3K) with LY294002 (25 µM) significantly potentiated an inhibitory effect of bFGF on TEER indicating that PI-3K signalling pathway counteracts bFGF modulation of TEER. In conclusion, we show that autocrine bFGF secretion is necessary for the proper barrier function of BCECs, whereas exogenous bFGF in higher doses suppresses barrier resistance. Our findings demonstrate a dual role for bFGF in the regulation of BCEC barrier function.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Encéfalo
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Capilares
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Factor 2 de Crecimiento de Fibroblastos
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Células Endoteliales
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Células Madre Pluripotentes Inducidas
Tipo de estudio:
Guideline
Límite:
Humans
Idioma:
En
Revista:
J Cell Physiol
Año:
2021
Tipo del documento:
Article
País de afiliación:
Lituania