Features of blood-brain barrier formation affected by the modulation of HIF activity in astroglial and neuronal cells in vitro


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Barriergenesis is the process of maturation of the primary vascular network of the brain responsible for the establishment of the blood-brain barrier. It represents a combination of factors that, on the one hand, contribute to the process of migration and tubulogenesis of endothelial cells (angiogenesis), on the other hand, contribute to the formation of new connections between endothelial cells and other elements of the neurovascular unit. Astrocytes play a key role in barriergenesis, however, mechanisms of their action are still poorly examined. We have studied the effects of HIF-1 modulators acting on the cells of non-endothelial origin (neurons and astrocytes) on the development of the blood-brain barrier in vitro. Application of FM19G11 regulating expression of HIF-1 activity and GSI-1 suppressing gamma-secretase and/or proteasomal activity resulted in the elevated expression of thrombospondins and matrix metalloproteinases in the developing blood-brain barrier. However, it caused the opposite effect on VEGF expression thus promoting barrier maturation in vitro.

作者简介

V. Ruzaeva

Voino-Yasenetsky Krasnoyarsk State Medical University

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Email: Veronikaruz@mail.ru
俄罗斯联邦, ul. Partizana Zheleznyaka 1, Krasnoyarsk, 660022

A. Morgun

Voino-Yasenetsky Krasnoyarsk State Medical University

Email: Veronikaruz@mail.ru
俄罗斯联邦, ul. Partizana Zheleznyaka 1, Krasnoyarsk, 660022

E. Khilazheva

Voino-Yasenetsky Krasnoyarsk State Medical University

Email: Veronikaruz@mail.ru
俄罗斯联邦, ul. Partizana Zheleznyaka 1, Krasnoyarsk, 660022

N. Kuvacheva

Voino-Yasenetsky Krasnoyarsk State Medical University

Email: Veronikaruz@mail.ru
俄罗斯联邦, ul. Partizana Zheleznyaka 1, Krasnoyarsk, 660022

E. Pozhilenkova

Voino-Yasenetsky Krasnoyarsk State Medical University

Email: Veronikaruz@mail.ru
俄罗斯联邦, ul. Partizana Zheleznyaka 1, Krasnoyarsk, 660022

E. Boitsova

Voino-Yasenetsky Krasnoyarsk State Medical University

Email: Veronikaruz@mail.ru
俄罗斯联邦, ul. Partizana Zheleznyaka 1, Krasnoyarsk, 660022

G. Martynova

Voino-Yasenetsky Krasnoyarsk State Medical University

Email: Veronikaruz@mail.ru
俄罗斯联邦, ul. Partizana Zheleznyaka 1, Krasnoyarsk, 660022

T. Taranushenko

Voino-Yasenetsky Krasnoyarsk State Medical University

Email: Veronikaruz@mail.ru
俄罗斯联邦, ul. Partizana Zheleznyaka 1, Krasnoyarsk, 660022

A. Salmina

Voino-Yasenetsky Krasnoyarsk State Medical University

Email: Veronikaruz@mail.ru
俄罗斯联邦, ul. Partizana Zheleznyaka 1, Krasnoyarsk, 660022

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