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

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 res...

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Detalles Bibliográficos
Autores principales: Zhang, Hongyu, Chen, Jian, Wang, Hailong, Lu, Xin, Li, Kai, Yang, Chao, Wu, Feng, Xu, Zihan, Nie, Huan, Ding, Bai, Guo, Zhifeng, Li, Yu, Wang, Jinfu, Li, Yinghui, Dai, Zhongquan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7461998/
https://www.ncbi.nlm.nih.gov/pubmed/33013433
http://dx.doi.org/10.3389/fphys.2020.00939
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author Zhang, Hongyu
Chen, Jian
Wang, Hailong
Lu, Xin
Li, Kai
Yang, Chao
Wu, Feng
Xu, Zihan
Nie, Huan
Ding, Bai
Guo, Zhifeng
Li, Yu
Wang, Jinfu
Li, Yinghui
Dai, Zhongquan
author_facet Zhang, Hongyu
Chen, Jian
Wang, Hailong
Lu, Xin
Li, Kai
Yang, Chao
Wu, Feng
Xu, Zihan
Nie, Huan
Ding, Bai
Guo, Zhifeng
Li, Yu
Wang, Jinfu
Li, Yinghui
Dai, Zhongquan
author_sort Zhang, Hongyu
collection PubMed
description 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.
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spelling pubmed-74619982020-10-01 Serum Metabolomics Associating With Circulating MicroRNA Profiles Reveal the Role of miR-383-5p in Rat Hippocampus Under Simulated Microgravity Zhang, Hongyu Chen, Jian Wang, Hailong Lu, Xin Li, Kai Yang, Chao Wu, Feng Xu, Zihan Nie, Huan Ding, Bai Guo, Zhifeng Li, Yu Wang, Jinfu Li, Yinghui Dai, Zhongquan Front Physiol Physiology 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. Frontiers Media S.A. 2020-08-18 /pmc/articles/PMC7461998/ /pubmed/33013433 http://dx.doi.org/10.3389/fphys.2020.00939 Text en Copyright © 2020 Zhang, Chen, Wang, Lu, Li, Yang, Wu, Xu, Nie, Ding, Guo, Li, Wang, Li and Dai. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Physiology
Zhang, Hongyu
Chen, Jian
Wang, Hailong
Lu, Xin
Li, Kai
Yang, Chao
Wu, Feng
Xu, Zihan
Nie, Huan
Ding, Bai
Guo, Zhifeng
Li, Yu
Wang, Jinfu
Li, Yinghui
Dai, Zhongquan
Serum Metabolomics Associating With Circulating MicroRNA Profiles Reveal the Role of miR-383-5p in Rat Hippocampus Under Simulated Microgravity
title Serum Metabolomics Associating With Circulating MicroRNA Profiles Reveal the Role of miR-383-5p in Rat Hippocampus Under Simulated Microgravity
title_full Serum Metabolomics Associating With Circulating MicroRNA Profiles Reveal the Role of miR-383-5p in Rat Hippocampus Under Simulated Microgravity
title_fullStr Serum Metabolomics Associating With Circulating MicroRNA Profiles Reveal the Role of miR-383-5p in Rat Hippocampus Under Simulated Microgravity
title_full_unstemmed Serum Metabolomics Associating With Circulating MicroRNA Profiles Reveal the Role of miR-383-5p in Rat Hippocampus Under Simulated Microgravity
title_short Serum Metabolomics Associating With Circulating MicroRNA Profiles Reveal the Role of miR-383-5p in Rat Hippocampus Under Simulated Microgravity
title_sort serum metabolomics associating with circulating microrna profiles reveal the role of mir-383-5p in rat hippocampus under simulated microgravity
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7461998/
https://www.ncbi.nlm.nih.gov/pubmed/33013433
http://dx.doi.org/10.3389/fphys.2020.00939
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