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miRNA‐182/Deptor/mTOR axis regulates autophagy to reduce intestinal ischaemia/reperfusion injury

It had been reported miR‐182 was down‐regulated after intestinal ischaemia/reperfusion (I/R) damage. However, its role and potential mechanisms are still unknown. This study was aimed to elucidate the function of miR‐182 in intestinal I/R injury and the underlying mechanisms. The model of intestinal...

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Autores principales: Li, Yunsheng, Luo, Yanhua, Li, Baochuan, Niu, Lijun, Liu, Jiaxin, Duan, Xiaoyun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7348187/
https://www.ncbi.nlm.nih.gov/pubmed/32510855
http://dx.doi.org/10.1111/jcmm.15420
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author Li, Yunsheng
Luo, Yanhua
Li, Baochuan
Niu, Lijun
Liu, Jiaxin
Duan, Xiaoyun
author_facet Li, Yunsheng
Luo, Yanhua
Li, Baochuan
Niu, Lijun
Liu, Jiaxin
Duan, Xiaoyun
author_sort Li, Yunsheng
collection PubMed
description It had been reported miR‐182 was down‐regulated after intestinal ischaemia/reperfusion (I/R) damage. However, its role and potential mechanisms are still unknown. This study was aimed to elucidate the function of miR‐182 in intestinal I/R injury and the underlying mechanisms. The model of intestinal injury was constructed in wild‐type and Deptor knockout (KO) mice. Haematoxylin‐eosin staining, Chiu's score and diamine oxidase were utilized to detect intestinal damage. RT‐qPCR assay was used to detected miR‐182 expression. Electronic microscopy was used to detect autophagosome. Western blot was applied to detect the expression of Deptor, S6/pS6, LC3‐II/LC3‐I and p62. Dual‐luciferase reporter assay was used to verify the relationship between miR‐182 and Deptor. The results showed miR‐182 was down‐regulated following intestinal I/R. Up‐regulation of miR‐182 reduced intestinal damage, autophagy, Deptor expression and enhanced mTOR activity following intestinal I/R. Moreover, suppression of autophagy reduced intestinal damage and inhibition of mTOR by rapamycin aggravated intestinal damage following intestinal I/R. Besides, damage of intestine was reduced and mTOR activity was enhanced in Deptor KO mice. In addition, Deptor was the target gene of miR‐182 and was indispensable for the protection of miR‐182 on intestine under I/R condition. Together, our research implicated up‐regulation of miR‐182 inhibited autophagy to alleviate intestinal I/R injury via mTOR by targeting Deptor.
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spelling pubmed-73481872020-07-14 miRNA‐182/Deptor/mTOR axis regulates autophagy to reduce intestinal ischaemia/reperfusion injury Li, Yunsheng Luo, Yanhua Li, Baochuan Niu, Lijun Liu, Jiaxin Duan, Xiaoyun J Cell Mol Med Original Articles It had been reported miR‐182 was down‐regulated after intestinal ischaemia/reperfusion (I/R) damage. However, its role and potential mechanisms are still unknown. This study was aimed to elucidate the function of miR‐182 in intestinal I/R injury and the underlying mechanisms. The model of intestinal injury was constructed in wild‐type and Deptor knockout (KO) mice. Haematoxylin‐eosin staining, Chiu's score and diamine oxidase were utilized to detect intestinal damage. RT‐qPCR assay was used to detected miR‐182 expression. Electronic microscopy was used to detect autophagosome. Western blot was applied to detect the expression of Deptor, S6/pS6, LC3‐II/LC3‐I and p62. Dual‐luciferase reporter assay was used to verify the relationship between miR‐182 and Deptor. The results showed miR‐182 was down‐regulated following intestinal I/R. Up‐regulation of miR‐182 reduced intestinal damage, autophagy, Deptor expression and enhanced mTOR activity following intestinal I/R. Moreover, suppression of autophagy reduced intestinal damage and inhibition of mTOR by rapamycin aggravated intestinal damage following intestinal I/R. Besides, damage of intestine was reduced and mTOR activity was enhanced in Deptor KO mice. In addition, Deptor was the target gene of miR‐182 and was indispensable for the protection of miR‐182 on intestine under I/R condition. Together, our research implicated up‐regulation of miR‐182 inhibited autophagy to alleviate intestinal I/R injury via mTOR by targeting Deptor. John Wiley and Sons Inc. 2020-06-08 2020-07 /pmc/articles/PMC7348187/ /pubmed/32510855 http://dx.doi.org/10.1111/jcmm.15420 Text en © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Li, Yunsheng
Luo, Yanhua
Li, Baochuan
Niu, Lijun
Liu, Jiaxin
Duan, Xiaoyun
miRNA‐182/Deptor/mTOR axis regulates autophagy to reduce intestinal ischaemia/reperfusion injury
title miRNA‐182/Deptor/mTOR axis regulates autophagy to reduce intestinal ischaemia/reperfusion injury
title_full miRNA‐182/Deptor/mTOR axis regulates autophagy to reduce intestinal ischaemia/reperfusion injury
title_fullStr miRNA‐182/Deptor/mTOR axis regulates autophagy to reduce intestinal ischaemia/reperfusion injury
title_full_unstemmed miRNA‐182/Deptor/mTOR axis regulates autophagy to reduce intestinal ischaemia/reperfusion injury
title_short miRNA‐182/Deptor/mTOR axis regulates autophagy to reduce intestinal ischaemia/reperfusion injury
title_sort mirna‐182/deptor/mtor axis regulates autophagy to reduce intestinal ischaemia/reperfusion injury
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7348187/
https://www.ncbi.nlm.nih.gov/pubmed/32510855
http://dx.doi.org/10.1111/jcmm.15420
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