PhD Scientific Days 2025

Poster Session I. - A: Molecular Medicine

Role of microRNAs in the cellular response to oxygen deficiency one month after sublethal hypoxic exposure in animals with high and low hypoxia tolerance

Name of the presenter

Silina Maria

Institute/workplace of the presenter

Petrovsky National Research Centre of Surgery

Authors

Silina Maria¹, Dzhalilova Dzhuliia¹, Mayak Margarita¹, Tsvetkov Ivan¹

1: Petrovsky National Research Centre of Surgery

Text of the abstract

The problem of adaptation to hypoxia and its role in the development of various diseases was studied on animals with different tolerances, whereas the most common way to determine which is sublethal hypoxia exposure (SHE) in a ventilated decompression chamber. More than 100 miRNAs were revealed as associating with the cellular response to hypoxia, and their role in the regulation of this process is due to the effect on mRNA of genes encoding isoforms of HIF (Hypoxia-Inducible Factor). However, the molecular mechanisms of hypoxia adaptation regulation at the miRNA level in connection to oxygen deficiency tolerance was not described in the literature.
The aim of this study was to characterize the role of miRNAs in the cellular response to SHE in animals with different hypoxia tolerance.
The study was performed on male Wistar rats aged 2-3 months (n=30). Before SHE, 1 ml of blood was obtained from the tail vein to take leukocytes. One month later, rats were tested for tolerance to oxygen deficiency by SHE (“altitude” 11500 m) once. According to the time to lateral position achievement, corresponding to the “gasping time” (GT), 2 groups of rats were distinguished - tolerant (TH, n=6, GT>240 s) and susceptible (SH, n=6, GT>80 s). Animals were removed from the experiment one month after SHE. The expression of Hif1a, Epas1, Hif3a, Arnt, Egln1 genes and miRNAs miR-210, miR-107, miR-145, miR-155 in leukocytes was evaluated by qRT-PCR. Differences between groups were evaluated using the nonparametric Mann-Whitney test and were considered statistically significant at p<0.05.
One month after a SHE, mRNA expression levels of Hif1a, Epas1, Hif3a, Arnt, and Egln1 were higher in blood cells regardless of oxygen deficiency tolerance in comparison to the pre-exposure levels. Only in TH animals decreased expression levels of miR-210 (activated by HIF-1α and HIF-2α) were detected, while in SH animals increased expression levels of miR-145 (Epas1 translation inhibitor) after SHE compared to pre-exposure values, indicating a rapid adaptation rate to hypoxia in TH rats.
The effect of SHE on animals with different oxygen deficiency tolerance persists for at least 1 month after it. The obtained data could serve as a basis for the non-invasive method development for determining hypoxia tolerance in laboratory animals.
This work was financially supported by the RSF (№25-25-00061).