Serum Metabolomics Associating With Circulating MicroRNA Profiles Reveal the Role of miR-383-5p in Rat Hippocampus Under Simulated Microgravity

Frontiers in Physiology

Jian Chen¹  Zhifeng Guo¹  Jinfu Wang¹  Xin Lu²  Huan Nie²  Yu Li²  Bai Ding³  Kai Li³  Zhongquan Dai³  Hailong Wang³  Feng Wu³  Zihan Xu³  Hongyu Zhang³  Chao Yang³  Yinghui Li³ 

[1] Institute of Cell and Developmental Biology, College of Life Sciences, Zhejiang University, Hangzhou, China;School of Life Sciences and Technology, Harbin Institute of Technology, Harbin, China;State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing, China;

关键词: microgravity;    metabolome;    miRNAome;    miR-383-5p;    aquaporin 4;    hippocampus;   

DOI  :  10.3389/fphys.2020.00939

来源: DOAJ

【 摘 要 】

Microgravity impacts various aspects of human health. Yet the mechanisms of spaceflight-induced health problems are not elucidated. Here, we mapped the fusion systemic analysis of the serum metabolome and the circulating microRNAome in a hindlimb unloading rat model to simulate microgravity. The response of serum metabolites and microRNAs to simulated microgravity was striking. Integrated pathway analysis of altered serum metabolites and target genes of the significantly altered circulating miRNAs with Integrated Molecular Pathway-Level Analysis (IMPaLA) software was mainly suggestive of modulation of neurofunctional signaling pathways. Particularly, we revealed significantly increased miR-383-5p and decreased aquaporin 4 (AQP4) in the hippocampus. Using rabies virus glycoprotein–modified exosomes, delivery of miR-383-5p inhibited the expression of AQP4 not only in rat C6 glioma cells in vitro but also in the hippocampus in vivo. Using bioinformatics to map the crosstalk between the circulating metabolome and miRNAome could offer opportunities to understand complex biological systems under microgravity. Our present results suggested that the change of miR-383-5p level and its regulation of target gene AQP4 was one of the potential molecular mechanisms of microgravity-induced cognitive impairment in the hippocampus.

【 授权许可】

Unknown