Exosomal miR-34b-3p upregulated in response to hypoxia preconditioning modulates circadian rhythms through the targeting of Clock.

Abstract

The relationship between circadian rhythm disorders and the development of various diseases appears to be significant, with limited current interventions available. Research literature suggests that hypoxia may influence the expression of clock genes and the shifting of rhythm phases. However, the precise mechanisms underlying the modulation of circadian rhythm through circulating exosomes by hypoxia preconditioning remain unclear. In this study, the mice were exposed to hypobaric conditions, simulating an altitude of 5000 m, for 1 h daily over the course of 1 week in order to achieve hypoxia preconditioning. Compared to the control group, no significant alteration was observed in the concentration, modal size, and mean size of circulating exosomes in hypoxia preconditioning mice. Exosomes derived from hypoxia preconditioning effectively suppressed the expression of Per1, Clock, and Bmal1 in NIH 3T3 cells. The miRNA sequencing analysis revealed miR-34b-3p as a potential regulator of the Clock, resulting in the downregulation of clock gene expression and subsequent promotion of proliferation and migration in NIH 3T3 cells. This study elucidated a novel mechanism of hypoxia preconditioning in the regulation of circadian rhythm, proposing that exosomal miR-34b-3p functions as an unrecognized molecule entity involved in the modulation of circadian rhythm. These findings offer a new avenue for developing protective strategies and therapeutic targets for circadian rhythm disorders.