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MiR-1-3p and MiR-124-3p Synergistically Damage the Intestinal Barrier in the Ageing Colon
BACKGROUND AND AIMS: Disruption of the intestinal barrier of the digestive tract is a common pathophysiological change in the elderly, which may partly contribute to gut dysfunction and inflammatory bowel disease [IBD]. This study aimed to discover new interactive epigenetic regulation patterns invo...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9089420/ https://www.ncbi.nlm.nih.gov/pubmed/34628497 http://dx.doi.org/10.1093/ecco-jcc/jjab179 |
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author | Sun, Ting-yi Li, Ya-qi Zhao, Fu-qian Sun, Hai-mei Gao, Yang Wu, Bo Yang, Shu Ji, Feng-qing Zhou, De-shan |
author_facet | Sun, Ting-yi Li, Ya-qi Zhao, Fu-qian Sun, Hai-mei Gao, Yang Wu, Bo Yang, Shu Ji, Feng-qing Zhou, De-shan |
author_sort | Sun, Ting-yi |
collection | PubMed |
description | BACKGROUND AND AIMS: Disruption of the intestinal barrier of the digestive tract is a common pathophysiological change in the elderly, which may partly contribute to gut dysfunction and inflammatory bowel disease [IBD]. This study aimed to discover new interactive epigenetic regulation patterns involved in intestinal barrier dysfunction and colitis in elderly populations. METHODS: Intestinal barrier function and structure were evaluated in naturally ageing mice and elderly people. High-throughput analysis was performed on colonic tissues from humans and mice. The synergistic roles of miR-1-3p and miR-124-3p were identified using microRNA mimic/agomirs. Related genes were examined in biopsies of old IBD patients. RESULTS: A defective mucus barrier was observed before mucosal microstructural damage during ageing. Elevated miR-1-3p expression in the colons of older individuals impaired the mucus barrier by directly targeting T-synthase, similarly to the mechanism of miR-124-3p, which we reported previously. Importantly, the synergistic effect of a half dose of each microRNA supplement on T-synthase and CDK4/6 was stronger than that of a full dose of miR-1-3p or miR-124-3p alone, and mice co-treated with two microRNAs showed greater susceptibility to chemical-induced colitis than mice treated with either microRNA alone. These two microRNAs were up-expressed in old IBD patients. CONCLUSIONS: The slight increases in miR-1-3p and miR-124-3p expression with ageing may be important contributors to the breakdown of intestinal homeostasis by targeting divergent genes in different cells. These data reveal the potential ability of multiple microRNAs to exert synergistic effects to damage the intestinal barrier and promote inflammatory bowel disease development in elderly populations. |
format | Online Article Text |
id | pubmed-9089420 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-90894202022-05-11 MiR-1-3p and MiR-124-3p Synergistically Damage the Intestinal Barrier in the Ageing Colon Sun, Ting-yi Li, Ya-qi Zhao, Fu-qian Sun, Hai-mei Gao, Yang Wu, Bo Yang, Shu Ji, Feng-qing Zhou, De-shan J Crohns Colitis Original Articles BACKGROUND AND AIMS: Disruption of the intestinal barrier of the digestive tract is a common pathophysiological change in the elderly, which may partly contribute to gut dysfunction and inflammatory bowel disease [IBD]. This study aimed to discover new interactive epigenetic regulation patterns involved in intestinal barrier dysfunction and colitis in elderly populations. METHODS: Intestinal barrier function and structure were evaluated in naturally ageing mice and elderly people. High-throughput analysis was performed on colonic tissues from humans and mice. The synergistic roles of miR-1-3p and miR-124-3p were identified using microRNA mimic/agomirs. Related genes were examined in biopsies of old IBD patients. RESULTS: A defective mucus barrier was observed before mucosal microstructural damage during ageing. Elevated miR-1-3p expression in the colons of older individuals impaired the mucus barrier by directly targeting T-synthase, similarly to the mechanism of miR-124-3p, which we reported previously. Importantly, the synergistic effect of a half dose of each microRNA supplement on T-synthase and CDK4/6 was stronger than that of a full dose of miR-1-3p or miR-124-3p alone, and mice co-treated with two microRNAs showed greater susceptibility to chemical-induced colitis than mice treated with either microRNA alone. These two microRNAs were up-expressed in old IBD patients. CONCLUSIONS: The slight increases in miR-1-3p and miR-124-3p expression with ageing may be important contributors to the breakdown of intestinal homeostasis by targeting divergent genes in different cells. These data reveal the potential ability of multiple microRNAs to exert synergistic effects to damage the intestinal barrier and promote inflammatory bowel disease development in elderly populations. Oxford University Press 2021-10-10 /pmc/articles/PMC9089420/ /pubmed/34628497 http://dx.doi.org/10.1093/ecco-jcc/jjab179 Text en © The Author(s) 2021. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Original Articles Sun, Ting-yi Li, Ya-qi Zhao, Fu-qian Sun, Hai-mei Gao, Yang Wu, Bo Yang, Shu Ji, Feng-qing Zhou, De-shan MiR-1-3p and MiR-124-3p Synergistically Damage the Intestinal Barrier in the Ageing Colon |
title | MiR-1-3p and MiR-124-3p Synergistically Damage the Intestinal Barrier in the Ageing Colon |
title_full | MiR-1-3p and MiR-124-3p Synergistically Damage the Intestinal Barrier in the Ageing Colon |
title_fullStr | MiR-1-3p and MiR-124-3p Synergistically Damage the Intestinal Barrier in the Ageing Colon |
title_full_unstemmed | MiR-1-3p and MiR-124-3p Synergistically Damage the Intestinal Barrier in the Ageing Colon |
title_short | MiR-1-3p and MiR-124-3p Synergistically Damage the Intestinal Barrier in the Ageing Colon |
title_sort | mir-1-3p and mir-124-3p synergistically damage the intestinal barrier in the ageing colon |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9089420/ https://www.ncbi.nlm.nih.gov/pubmed/34628497 http://dx.doi.org/10.1093/ecco-jcc/jjab179 |
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