ORIGINAL RESEARCH

Hypoxia enhances transcytosis in intestinal enterocytes

Maltseva DV1, Shkurnikov MYu1,2, Nersisyan SA1, Nikulin SV1, Kurnosov AA1, Raigorodskaya MP3, Osipyants AI2,4, Tonevitsky EA5
About authors

1 National Research University Higher School of Economics, Moscow, Russia

2 P. A. Hertsen Moscow Oncology Research Center, branch of the National Medical Research Radiology Center, Moscow, Russia

3 SRC Bioclinicum, Moscow, Russia

4 Far Eastern Federal University, Vladivostok, Russia

5 Fund for Development of Innovative Scientific-Technological Center Mendeleev Valley, Moscow, Russia

Correspondence should be addressed: Diana V. Maltseva
Vavilova, 7, Moscow, 117321; moc.liamg@avestlamd

About paper

Funding: the study was supported by the Ministry of Science and Higher Education of the Russian Federation (Project ID RFMEFI61719X0056).

Acknowledgement: the authors thank the Human Proteome Core Facility (Institute of Biomedical Chemistry) for permission to use the Facility’s equipment.

Author contribution: Maltseva DV — molecular tests, analysis of their results, manuscript preparation; Shkurnikov MYu — analysis of transcriptome and sequencing data, statistical analysis; Nersisyan SA — sequencing data processing, bioinformatic analysis, functional gene analysis; Nikulin SV — cell culture, sample preparation for subsequent proteome analysis, proteomic data analysis; Kurnosov AA — sample preparation for microRNA sequencing, analysis of sequencing data; Raigorodskaya MP — real-time PCR-based analysis of gene expression, transcriptome analysis; Osipyants AI — cell culture, sample preparation for subsequent proteome and transcriptome analyses; Tonevitsky EA — supervision, data analysis, manuscript preparation.

Received: 2020-08-08 Accepted: 2020-08-21 Published online: 2020-08-28
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The integrity of the intestinal epithelial cell lining is crucial for the normal intestinal function. As a rule, intestinal inflammation is associated with additional tissue hypoxia, leading to the loss of epithelial monolayer integrity. However, in the absence of visible damage to the epithelium, there still might be a risk of infection driven by changes in the intracellular transport of bacteria-containing vesicles. The aim of this study was to investigate the effects of hypoxia on transcytosis using a human intestinal enterocyte model. We found that hypoxia enhances transcytosis of the model protein ricin 1.8-fold. The comparative transcriptome and proteome analyses revealed significant changes in the expression of genes involved in intracellular vesicle transport. Specifically, the expression of apoB (the regulator of lipid metabolism) was changed at both protein (6.5-fold) and mRNA (2.1-fold) levels. Further research is needed into the possible mechanism regulating gene expression in intestinal erythrocytes under hypoxic conditions.

Keywords: hypoxia, microRNA, enterocyte, intestinal epithelium, mRNA, proteome, transcriptome, transcytosis, Caco-2

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