MiR-181c-5p mediates apoptosis of vascular endothelial cells induced by hyperoxemia via ceRNA crosstalk

Jizhi Wu,Junfeng Ge,Guangqi Zhang,Yuguang Zhang,Hui Xiong,Gang Ding

doi:10.1038/s41598-021-95712-1

Abstract

Oxygen therapy has been widely used in clinical practice, especially in anesthesia and emergency medicine. However, the risks of hyperoxemia caused by excessive O2 supply have not been sufficiently appreciated. Because nasal inhalation is mostly used for oxygen therapy, the pulmonary capillaries are often the first to be damaged by hyperoxia, causing many serious consequences. Nevertheless, the molecular mechanism by which hyperoxia injures pulmonary capillary endothelial cells (LMECs) has not been fully elucidated. Therefore, we systematically investigated these issues using next-generation sequencing and functional research techniques by focusing on non-coding RNAs. Our results showed that hyperoxia significantly induced apoptosis and profoundly affected the transcriptome profiles of LMECs. Hyperoxia significantly up-regulated miR-181c-5p expression, while down-regulated the expressions of NCAPG and lncRNA-DLEU2 in LMECs. Moreover, LncRNA-DLEU2 could bind complementarily to miR-181c-5p and acted as a miRNA sponge to block the inhibitory effect of miR-181c-5p on its target gene NCAPG. The down-regulation of lncRNA-DLEU2 induced by hyperoxia abrogated its inhibition of miR-181c-5p function, which together with the hyperoxia-induced upregulation of miR-181c-5p, all these significantly decreased the expression of NCAPG, resulting in apoptosis of LMECs. Our results demonstrated a ceRNA network consisting of lncRNA-DLEU2, miR-181c-5p and NCAPG, which played an important role in hyperoxia-induced apoptosis of vascular endothelial injury. Our findings will contribute to the full understanding of the harmful effects of hyperoxia and to find ways for effectively mitigating its deleterious effects.

Highlights

Oxygen therapy using high-concentration or pure oxygen is a widely used therapeutic technique to correct hypoxemia in anesthesia and emergency m edicine[1]
The results showed that compared with LMECs in a normal culture environment, the apoptosis of LMECs treated with hyperoxia was significantly enhanced, especially after 24 h (Fig. S1a)
Many mRNAs regulated by hyperoxia were significantly correlated (p < 0.05, |R|> 0.5) or co-expressed with some significantly differentially expressed lncRNAs, which reflected the functional significance of these lncRNAs (Fig. 1c)

Summary

Introduction

Oxygen therapy using high-concentration or pure oxygen is a widely used therapeutic technique to correct hypoxemia in anesthesia and emergency m edicine[1]. The capillary endothelial cell injury induced by ROS leads to microcirculation disorders, hypotension, shock or even DIC9. These pathologies are important contributors to the damage of heart, brain, lung, and kidney, and even death caused by hypoxemia. ROS can regulate the expression of miRNAs and their functions through multiple mechanisms. The roles and mechanisms of miRNAs in the endothelial injury caused by hyperoxic oxidative stress, which is closely related to anesthesia, are still not fully elucidated. The studies on the role and mechanism of the lncRNA and ceRNA network in the hyperoxia-induced vascular endothelial cell injury are still in their infancy

Methods

Results

Conclusion