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Increased serum extracellular vesicle miR-144-3p and miR-486a-3p in a mouse model of adipose tissue regeneration promote hepatocyte proliferation by targeting Txnip

Adipose-derived stem cells are expected to be applied to regenerative medicine for various incurable diseases including liver cirrhosis. Although microRNAs contained in extracellular vesicles (EV-miRNAs) have been implicated in their regenerative effects, the precise mechanism has not been fully elu...

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Autores principales: Niitsu, Yoshihiro, Komiya, Chikara, Takeuchi, Akira, Hara, Kazunari, Horino, Masato, Aoki, Jun, Okazaki, Rei, Murakami, Masanori, Tsujimoto, Kazutaka, Ikeda, Kenji, Yamada, Tetsuya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10159167/
https://www.ncbi.nlm.nih.gov/pubmed/37141242
http://dx.doi.org/10.1371/journal.pone.0284989
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author Niitsu, Yoshihiro
Komiya, Chikara
Takeuchi, Akira
Hara, Kazunari
Horino, Masato
Aoki, Jun
Okazaki, Rei
Murakami, Masanori
Tsujimoto, Kazutaka
Ikeda, Kenji
Yamada, Tetsuya
author_facet Niitsu, Yoshihiro
Komiya, Chikara
Takeuchi, Akira
Hara, Kazunari
Horino, Masato
Aoki, Jun
Okazaki, Rei
Murakami, Masanori
Tsujimoto, Kazutaka
Ikeda, Kenji
Yamada, Tetsuya
author_sort Niitsu, Yoshihiro
collection PubMed
description Adipose-derived stem cells are expected to be applied to regenerative medicine for various incurable diseases including liver cirrhosis. Although microRNAs contained in extracellular vesicles (EV-miRNAs) have been implicated in their regenerative effects, the precise mechanism has not been fully elucidated. Tamoxifen-inducible adipocyte-specific insulin receptor knockout (iFIRKO) mice are known to exhibit acute adipose tissue regeneration with increased numbers of adipose stem and progenitor cells (ASPCs). Because adipose tissue is the major source of circulating EV-miRNAs, we investigated alterations in serum EV-miRNAs in iFIRKO mice. A comprehensive analysis using miRNA sequencing on serum EVs revealed that most EV-miRNAs were decreased due to the loss of mature adipocytes, but there were 19 EV-miRNAs that were increased in the serum of iFIRKO mice. Among them, miR-144-3p and miR-486a-3p were found to be increased in the liver as well as serum EVs. While the expression levels of pri-miR-144-3p and pri-miR-486a-3p were not increased in the liver, they were elevated in the adipose tissue, suggesting that these miRNAs may be delivered from ASPCs increased in the adipose tissue to the liver via EVs. Increased hepatocyte proliferation was observed in the liver of iFIRKO mice, and we found that both miR-144-3p and miR-486a-3p have a function to promote hepatocyte proliferation by suppressing Txnip expression as a target gene. miR-144-3p and miR-486a-3p can be candidate therapeutic tools for conditions requiring hepatocyte proliferation, such as liver cirrhosis, and our current study suggests that examining EV-miRNAs secreted in vivo may lead to the discovery of miRNAs involved in regenerative medicine that have not been identified by in vitro analysis.
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spelling pubmed-101591672023-05-05 Increased serum extracellular vesicle miR-144-3p and miR-486a-3p in a mouse model of adipose tissue regeneration promote hepatocyte proliferation by targeting Txnip Niitsu, Yoshihiro Komiya, Chikara Takeuchi, Akira Hara, Kazunari Horino, Masato Aoki, Jun Okazaki, Rei Murakami, Masanori Tsujimoto, Kazutaka Ikeda, Kenji Yamada, Tetsuya PLoS One Research Article Adipose-derived stem cells are expected to be applied to regenerative medicine for various incurable diseases including liver cirrhosis. Although microRNAs contained in extracellular vesicles (EV-miRNAs) have been implicated in their regenerative effects, the precise mechanism has not been fully elucidated. Tamoxifen-inducible adipocyte-specific insulin receptor knockout (iFIRKO) mice are known to exhibit acute adipose tissue regeneration with increased numbers of adipose stem and progenitor cells (ASPCs). Because adipose tissue is the major source of circulating EV-miRNAs, we investigated alterations in serum EV-miRNAs in iFIRKO mice. A comprehensive analysis using miRNA sequencing on serum EVs revealed that most EV-miRNAs were decreased due to the loss of mature adipocytes, but there were 19 EV-miRNAs that were increased in the serum of iFIRKO mice. Among them, miR-144-3p and miR-486a-3p were found to be increased in the liver as well as serum EVs. While the expression levels of pri-miR-144-3p and pri-miR-486a-3p were not increased in the liver, they were elevated in the adipose tissue, suggesting that these miRNAs may be delivered from ASPCs increased in the adipose tissue to the liver via EVs. Increased hepatocyte proliferation was observed in the liver of iFIRKO mice, and we found that both miR-144-3p and miR-486a-3p have a function to promote hepatocyte proliferation by suppressing Txnip expression as a target gene. miR-144-3p and miR-486a-3p can be candidate therapeutic tools for conditions requiring hepatocyte proliferation, such as liver cirrhosis, and our current study suggests that examining EV-miRNAs secreted in vivo may lead to the discovery of miRNAs involved in regenerative medicine that have not been identified by in vitro analysis. Public Library of Science 2023-05-04 /pmc/articles/PMC10159167/ /pubmed/37141242 http://dx.doi.org/10.1371/journal.pone.0284989 Text en © 2023 Niitsu et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Niitsu, Yoshihiro
Komiya, Chikara
Takeuchi, Akira
Hara, Kazunari
Horino, Masato
Aoki, Jun
Okazaki, Rei
Murakami, Masanori
Tsujimoto, Kazutaka
Ikeda, Kenji
Yamada, Tetsuya
Increased serum extracellular vesicle miR-144-3p and miR-486a-3p in a mouse model of adipose tissue regeneration promote hepatocyte proliferation by targeting Txnip
title Increased serum extracellular vesicle miR-144-3p and miR-486a-3p in a mouse model of adipose tissue regeneration promote hepatocyte proliferation by targeting Txnip
title_full Increased serum extracellular vesicle miR-144-3p and miR-486a-3p in a mouse model of adipose tissue regeneration promote hepatocyte proliferation by targeting Txnip
title_fullStr Increased serum extracellular vesicle miR-144-3p and miR-486a-3p in a mouse model of adipose tissue regeneration promote hepatocyte proliferation by targeting Txnip
title_full_unstemmed Increased serum extracellular vesicle miR-144-3p and miR-486a-3p in a mouse model of adipose tissue regeneration promote hepatocyte proliferation by targeting Txnip
title_short Increased serum extracellular vesicle miR-144-3p and miR-486a-3p in a mouse model of adipose tissue regeneration promote hepatocyte proliferation by targeting Txnip
title_sort increased serum extracellular vesicle mir-144-3p and mir-486a-3p in a mouse model of adipose tissue regeneration promote hepatocyte proliferation by targeting txnip
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10159167/
https://www.ncbi.nlm.nih.gov/pubmed/37141242
http://dx.doi.org/10.1371/journal.pone.0284989
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