Cargando…
Elimination of p19(ARF)‐expressing cells protects against pulmonary emphysema in mice
Senescent cells accumulate in tissues during aging and are considered to underlie several aging‐associated phenotypes and diseases. We recently reported that the elimination of p19(ARF)‐expressing senescent cells from lung tissue restored tissue function and gene expression in middle‐aged (12‐month‐...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6156494/ https://www.ncbi.nlm.nih.gov/pubmed/30058137 http://dx.doi.org/10.1111/acel.12827 |
_version_ | 1783358115693985792 |
---|---|
author | Mikawa, Ryuta Suzuki, Yohei Baskoro, Hario Kanayama, Kazuki Sugimoto, Kazushi Sato, Tadashi Sugimoto, Masataka |
author_facet | Mikawa, Ryuta Suzuki, Yohei Baskoro, Hario Kanayama, Kazuki Sugimoto, Kazushi Sato, Tadashi Sugimoto, Masataka |
author_sort | Mikawa, Ryuta |
collection | PubMed |
description | Senescent cells accumulate in tissues during aging and are considered to underlie several aging‐associated phenotypes and diseases. We recently reported that the elimination of p19(ARF)‐expressing senescent cells from lung tissue restored tissue function and gene expression in middle‐aged (12‐month‐old) mice. The aging of lung tissue increases the risk of pulmonary diseases such as emphysema, and cellular senescence is accelerated in emphysema patients. However, there is currently no direct evidence to show that cellular senescence promotes the pathology of emphysema, and the involvement of senescence in the development of this disease has yet to be clarified. We herein demonstrated that p19(ARF) facilitated the development of pulmonary emphysema in mice. The elimination of p19(ARF)‐expressing cells prevented lung tissue from elastase‐induced lung dysfunction. These effects appeared to depend on reduced pulmonary inflammation, which is enhanced after elastase stimulation. Furthermore, the administration of a senolytic drug that selectively kills senescent cells attenuated emphysema‐associated pathologies. These results strongly suggest the potential of senescent cells as therapeutic/preventive targets for pulmonary emphysema. |
format | Online Article Text |
id | pubmed-6156494 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-61564942018-10-01 Elimination of p19(ARF)‐expressing cells protects against pulmonary emphysema in mice Mikawa, Ryuta Suzuki, Yohei Baskoro, Hario Kanayama, Kazuki Sugimoto, Kazushi Sato, Tadashi Sugimoto, Masataka Aging Cell Original Articles Senescent cells accumulate in tissues during aging and are considered to underlie several aging‐associated phenotypes and diseases. We recently reported that the elimination of p19(ARF)‐expressing senescent cells from lung tissue restored tissue function and gene expression in middle‐aged (12‐month‐old) mice. The aging of lung tissue increases the risk of pulmonary diseases such as emphysema, and cellular senescence is accelerated in emphysema patients. However, there is currently no direct evidence to show that cellular senescence promotes the pathology of emphysema, and the involvement of senescence in the development of this disease has yet to be clarified. We herein demonstrated that p19(ARF) facilitated the development of pulmonary emphysema in mice. The elimination of p19(ARF)‐expressing cells prevented lung tissue from elastase‐induced lung dysfunction. These effects appeared to depend on reduced pulmonary inflammation, which is enhanced after elastase stimulation. Furthermore, the administration of a senolytic drug that selectively kills senescent cells attenuated emphysema‐associated pathologies. These results strongly suggest the potential of senescent cells as therapeutic/preventive targets for pulmonary emphysema. John Wiley and Sons Inc. 2018-07-30 2018-10 /pmc/articles/PMC6156494/ /pubmed/30058137 http://dx.doi.org/10.1111/acel.12827 Text en © 2018 The Authors. Aging Cell published by the Anatomical Society 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 Mikawa, Ryuta Suzuki, Yohei Baskoro, Hario Kanayama, Kazuki Sugimoto, Kazushi Sato, Tadashi Sugimoto, Masataka Elimination of p19(ARF)‐expressing cells protects against pulmonary emphysema in mice |
title | Elimination of p19(ARF)‐expressing cells protects against pulmonary emphysema in mice |
title_full | Elimination of p19(ARF)‐expressing cells protects against pulmonary emphysema in mice |
title_fullStr | Elimination of p19(ARF)‐expressing cells protects against pulmonary emphysema in mice |
title_full_unstemmed | Elimination of p19(ARF)‐expressing cells protects against pulmonary emphysema in mice |
title_short | Elimination of p19(ARF)‐expressing cells protects against pulmonary emphysema in mice |
title_sort | elimination of p19(arf)‐expressing cells protects against pulmonary emphysema in mice |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6156494/ https://www.ncbi.nlm.nih.gov/pubmed/30058137 http://dx.doi.org/10.1111/acel.12827 |
work_keys_str_mv | AT mikawaryuta eliminationofp19arfexpressingcellsprotectsagainstpulmonaryemphysemainmice AT suzukiyohei eliminationofp19arfexpressingcellsprotectsagainstpulmonaryemphysemainmice AT baskorohario eliminationofp19arfexpressingcellsprotectsagainstpulmonaryemphysemainmice AT kanayamakazuki eliminationofp19arfexpressingcellsprotectsagainstpulmonaryemphysemainmice AT sugimotokazushi eliminationofp19arfexpressingcellsprotectsagainstpulmonaryemphysemainmice AT satotadashi eliminationofp19arfexpressingcellsprotectsagainstpulmonaryemphysemainmice AT sugimotomasataka eliminationofp19arfexpressingcellsprotectsagainstpulmonaryemphysemainmice |