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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...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2020
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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. |
format | Online Article Text |
id | pubmed-7461998 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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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