miR-142 induces accumulation of reactive oxygen species (ROS) by inhibiting pexophagy in aged bone marrow mesenchymal stem cells

Elevation of the levels of reactive oxygen species (ROS) is a major tissue-degenerative phenomenon involved in aging and aging-related diseases. The detailed mechanisms underlying aging-related ROS generation remain unclear. Presently, the expression of microRNA (miR)-142-5p was significantly upregu...

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Autores principales: Houri, Kei, Mori, Tatsufumi, Onodera, Yuta, Tsujimoto, Takatoshi, Takehara, Toshiyuki, Nakao, Shinichi, Teramura, Takeshi, Fukuda, Kanji
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
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Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7048811/
https://www.ncbi.nlm.nih.gov/pubmed/32111926
http://dx.doi.org/10.1038/s41598-020-60346-2
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author Houri, Kei
Mori, Tatsufumi
Onodera, Yuta
Tsujimoto, Takatoshi
Takehara, Toshiyuki
Nakao, Shinichi
Teramura, Takeshi
Fukuda, Kanji
author_facet Houri, Kei
Mori, Tatsufumi
Onodera, Yuta
Tsujimoto, Takatoshi
Takehara, Toshiyuki
Nakao, Shinichi
Teramura, Takeshi
Fukuda, Kanji
author_sort Houri, Kei
collection PubMed
description Elevation of the levels of reactive oxygen species (ROS) is a major tissue-degenerative phenomenon involved in aging and aging-related diseases. The detailed mechanisms underlying aging-related ROS generation remain unclear. Presently, the expression of microRNA (miR)-142-5p was significantly upregulated in bone marrow mesenchymal stem cells (BMMSCs) of aged mice. Overexpression of miR-142 and subsequent observation revealed that miR-142 involved ROS accumulation through the disruption of selective autophagy for peroxisomes (pexophagy). Mechanistically, attenuation of acetyltransferase Ep300 triggered the upregulation of miR-142 in aged BMMSCs, and miR-142 targeted endothelial PAS domain protein 1 (Epas1) was identified as a regulatory protein of pexophagy. These findings support a novel molecular mechanism relating aging-associated ROS generation and organelle degradation in BMMSCs, and suggest a potential therapeutic target for aging-associated disorders that are accompanied by stem cell degeneration.
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spelling pubmed-70488112020-03-06 miR-142 induces accumulation of reactive oxygen species (ROS) by inhibiting pexophagy in aged bone marrow mesenchymal stem cells Houri, Kei Mori, Tatsufumi Onodera, Yuta Tsujimoto, Takatoshi Takehara, Toshiyuki Nakao, Shinichi Teramura, Takeshi Fukuda, Kanji Sci Rep Article Elevation of the levels of reactive oxygen species (ROS) is a major tissue-degenerative phenomenon involved in aging and aging-related diseases. The detailed mechanisms underlying aging-related ROS generation remain unclear. Presently, the expression of microRNA (miR)-142-5p was significantly upregulated in bone marrow mesenchymal stem cells (BMMSCs) of aged mice. Overexpression of miR-142 and subsequent observation revealed that miR-142 involved ROS accumulation through the disruption of selective autophagy for peroxisomes (pexophagy). Mechanistically, attenuation of acetyltransferase Ep300 triggered the upregulation of miR-142 in aged BMMSCs, and miR-142 targeted endothelial PAS domain protein 1 (Epas1) was identified as a regulatory protein of pexophagy. These findings support a novel molecular mechanism relating aging-associated ROS generation and organelle degradation in BMMSCs, and suggest a potential therapeutic target for aging-associated disorders that are accompanied by stem cell degeneration. Nature Publishing Group UK 2020-02-28 /pmc/articles/PMC7048811/ /pubmed/32111926 http://dx.doi.org/10.1038/s41598-020-60346-2 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Houri, Kei
Mori, Tatsufumi
Onodera, Yuta
Tsujimoto, Takatoshi
Takehara, Toshiyuki
Nakao, Shinichi
Teramura, Takeshi
Fukuda, Kanji
miR-142 induces accumulation of reactive oxygen species (ROS) by inhibiting pexophagy in aged bone marrow mesenchymal stem cells
title miR-142 induces accumulation of reactive oxygen species (ROS) by inhibiting pexophagy in aged bone marrow mesenchymal stem cells
title_full miR-142 induces accumulation of reactive oxygen species (ROS) by inhibiting pexophagy in aged bone marrow mesenchymal stem cells
title_fullStr miR-142 induces accumulation of reactive oxygen species (ROS) by inhibiting pexophagy in aged bone marrow mesenchymal stem cells
title_full_unstemmed miR-142 induces accumulation of reactive oxygen species (ROS) by inhibiting pexophagy in aged bone marrow mesenchymal stem cells
title_short miR-142 induces accumulation of reactive oxygen species (ROS) by inhibiting pexophagy in aged bone marrow mesenchymal stem cells
title_sort mir-142 induces accumulation of reactive oxygen species (ros) by inhibiting pexophagy in aged bone marrow mesenchymal stem cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7048811/
https://www.ncbi.nlm.nih.gov/pubmed/32111926
http://dx.doi.org/10.1038/s41598-020-60346-2
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