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.
Download PDF:
Keywords: blood-brain barrier, barriergenesis, neurovascular unit, angiogenesis, HIF-1 modulators
Citation:
Ruzaeva V.A., Morgun A.V., Khilazheva E.D., Kuvacheva N.V., Pozhilenkova E.A., Boitsova E.B., Martynova G.P., Taranushenko T.E., Salmina A.B. (2016) Development of blood-brain barrier under the modulation of HIF activity in astroglial and neuronal cells in vitro. Biomeditsinskaya Khimiya, 62(6), 664-669.
Ruzaeva V.A. et al. Development of blood-brain barrier under the modulation of HIF activity in astroglial and neuronal cells in vitro // Biomeditsinskaya Khimiya. - 2016. - V. 62. -N 6. - P. 664-669.
Ruzaeva V.A. et al., "Development of blood-brain barrier under the modulation of HIF activity in astroglial and neuronal cells in vitro." Biomeditsinskaya Khimiya 62.6 (2016): 664-669.
Ruzaeva, V. A., Morgun, A. V., Khilazheva, E. D., Kuvacheva, N. V., Pozhilenkova, E. A., Boitsova, E. B., Martynova, G. P., Taranushenko, T. E., Salmina, A. B. (2016). Development of blood-brain barrier under the modulation of HIF activity in astroglial and neuronal cells in vitro. Biomeditsinskaya Khimiya, 62(6), 664-669.
Qiang L., Wu T., Zhang H.-W., Lu N., Hu R., Wang Y.-J., Zhao L., Chen F.-H., Wang X.-T., You Q.-D.,Guo Q.-L. (2012) Cell Death and Differentiation, 19, 284-294. CrossRef Scholar google search
Moreno-Manzano V., Rodríguez-Jiménez F.J., Aceña-Bonilla J.L., Fustero-Lardíes S., Erceg S., Dopazo J., Montaner D., Stojkovic M., Sánchez-Puelles J.M. (2010) J. Biol. Chem., 285(2), 1333-1342. Scholar google search
Assar M. El., Sánchez-Puelles J.M., Royo I., López-Hernández E., Sánchez-Ferrer A., Aceña J.L., Rodríguez-Mañas L., Angulo J. (2015) Br. J. Pharmacol., 172(5), 1277-1291. Scholar google search
Villa J.C., Chiu D., Brandes A.H., Escorcia F.E., Villa C.H., Maguire W.F., Hu C.J., de Stanchina E., Simon M.C., Sisodia S.S., Scheinberg D.A., Li Y.M. (2014) Cell Rep., 8(4), 1077-1092. CrossRef Scholar google search
Weidemann A., Krohne T.U., Aguilar E., Kurihara T., Takeda N., Dorrell M.I., Simon M.C., Haase V.H., Friedlander M., Johnson R.S. (2010)Glia, 58(10), 1177-1185. Scholar google search
Gustafsson M.V., Zheng X., Pereira T., Gradin K., Jin S., Lundkvist J., Ruas J.L., Poellinger L., Lendahl U., Bondesson M. (2005) Dev. Cell, 9(5), 617-628. CrossRef Scholar google search
