Abstract
Weightlessness-induced cardiovascular dysfunction can lead to physiological and pathological consequences. It has been shown that spaceflight or simulated microgravity can alter expression profiles of some microRNAs (miRNAs). Here, we attempt to identify the role of miRNAs in human umbilical vein endothelial cells (HUVECs) apoptosis under simulated microgravity. RNA-sequencing and quantitative real-time PCR (qRT-PCR) assays were used to identify differentially expressed miRNAs in HUVECs under simulated microgravity. Then we obtained the target genes of these miRNAs through target analysis software. Moreover, GO and KEGG enrichment analysis were performed. The effects of these miRNAs on HUVECs apoptosis were evaluated by flow cytometry, Western blot and Hoechst staining. Furthermore, we obtained the target gene of miR-27b-5p by luciferase assay, qRT-PCR and Western blot. Finally, we investigated the relationship between this target gene and miR-27b-5p in HUVECs apoptosis under normal gravity or simulated microgravity. We found 29 differentially expressed miRNAs in HUVECs under simulated microgravity. Of them, the expressions of 3 miRNAs were validated by qRT-PCR. We demonstrated that miR-27b-5p affected HUVECs apoptosis by inhibiting zinc fingers and homeoboxes 1 (ZHX1). Our results reported here demonstrate for the first time that simulated microgravity can alter the expression of some miRNAs in HUVECs and miR-27b-5p may protect HUVECs from apoptosis under simulated microgravity by targeting ZHX1.
Highlights
Weightlessness is a particular environment that can cause stress and subsequent adaption in the human body
Results miRNAs expression changes under simulated microgravity in human umbilical vein endothelial cells (HUVECs) miRNAs were previously demonstrated to be regulated by weightlessness and involved in gene expressions
The major hypothesis of this study is that ground-based simulated microgravity would alter miRNAs expression profiles in HUVECs and differentially expressed miRNAs would take part in apoptosis of HUVECs
Summary
Weightlessness is a particular environment that can cause stress and subsequent adaption in the human body. Numerous studies have shown that real or simulated microgravity environment can lead to a high incidence of medical conditions involving cardiovascular system [1], hematological system [2], cellular immune function [3], skeletal system [4], urinary system [5], etc. These alterations induced by weightlessness are harmful to the health, working performance and safety of the astronauts. Coupé et al certified that impairment of endotheliumdependent functions caused by prolonged bed rest at the microcirculation level and endothelium should be a target for countermeasures when exposure to weightlessness [9]
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