Oxyquinoline-Dependent Changes in Claudin-Encoding Genes Contribute to Impairment of the Barrier Function of the Trophoblast Monolayer
- Authors: Knyazev E.N.1, Petrov V.A.1, Gazizov I.N.1, Gerasimenko T.N.1, Tsypina I.M.1,2, Tonevitsky A.G.1,2, Sukhikh G.T.3
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Affiliations:
- BioClinicum Research Center
- National Research University Higher School of Economics
- V. I. Kulakov National Medical Research Center for Obstetrics, Gynecology, and Perinatology
- Issue: Vol 166, No 3 (2019)
- Pages: 369-372
- Section: Article
- URL: https://journals.rcsi.science/0007-4888/article/view/241015
- DOI: https://doi.org/10.1007/s10517-019-04352-z
- ID: 241015
Cite item
Abstract
Natural response to hypoxia critically depends on rapid stabilization of hypoxia-inducible factor (HIF). Under normoxic conditions, HIF-prolyl hydroxylases mark α-subunits of HIF for degradation, while hypoxia results in stabilization of HIF-α. Oxyquinoline derivatives suppress activity of HIF-prolyl hydroxylases leading to HIF activation in the cell. Here we show that 24-h incubation of BeWo b30 choriocarcinoma cells (a model of trophoblast in the placental barrier) with oxyquinoline derivative leads to a decrease in transepithelial electrical resistance (TEER) of the cell monolayer, while the permeability of the monolayer for FITC-dextran (70 kDa) remains unchanged. These findings suggest that the overall barrier function is preserved, while the structure of intercellular tight junctions can undergo minor changes. Using Affymetrix Human Transcriptome Array 2.0, we showed that the treatment with oxyquinoline derivative was followed by a decrease in the expression of claudins 6 and 7 (CLDN6, CLDN7), occludin (OCLN), contact adhesion molecule 3 (JAM3), and angiomotinlike protein 1 (AMOTL1).
About the authors
E. N. Knyazev
BioClinicum Research Center
Email: tonevitsky@mail.ru
Russian Federation, Moscow
V. A. Petrov
BioClinicum Research Center
Email: tonevitsky@mail.ru
Russian Federation, Moscow
I. N. Gazizov
BioClinicum Research Center
Email: tonevitsky@mail.ru
Russian Federation, Moscow
T. N. Gerasimenko
BioClinicum Research Center
Email: tonevitsky@mail.ru
Russian Federation, Moscow
I. M. Tsypina
BioClinicum Research Center; National Research University Higher School of Economics
Email: tonevitsky@mail.ru
Russian Federation, Moscow; Moscow
A. G. Tonevitsky
BioClinicum Research Center; National Research University Higher School of Economics
Author for correspondence.
Email: tonevitsky@mail.ru
Russian Federation, Moscow; Moscow
G. T. Sukhikh
V. I. Kulakov National Medical Research Center for Obstetrics, Gynecology, and Perinatology
Email: tonevitsky@mail.ru
Russian Federation, Moscow