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Peptidylarginine deiminase 4 promotes age-related organ fibrosis
Aging promotes inflammation, a process contributing to fibrosis and decline in organ function. The release of neutrophil extracellular traps (NETs [NETosis]), orchestrated by peptidylarginine deiminase 4 (PAD4), damages organs in acute inflammatory models. We determined that NETosis is more prevalen...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5294849/ https://www.ncbi.nlm.nih.gov/pubmed/28031479 http://dx.doi.org/10.1084/jem.20160530 |
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author | Martinod, Kimberly Witsch, Thilo Erpenbeck, Luise Savchenko, Alexander Hayashi, Hideki Cherpokova, Deya Gallant, Maureen Mauler, Maximilian Cifuni, Stephen M. Wagner, Denisa D. |
author_facet | Martinod, Kimberly Witsch, Thilo Erpenbeck, Luise Savchenko, Alexander Hayashi, Hideki Cherpokova, Deya Gallant, Maureen Mauler, Maximilian Cifuni, Stephen M. Wagner, Denisa D. |
author_sort | Martinod, Kimberly |
collection | PubMed |
description | Aging promotes inflammation, a process contributing to fibrosis and decline in organ function. The release of neutrophil extracellular traps (NETs [NETosis]), orchestrated by peptidylarginine deiminase 4 (PAD4), damages organs in acute inflammatory models. We determined that NETosis is more prevalent in aged mice and investigated the role of PAD4/NETs in age-related organ fibrosis. Reduction in fibrosis was seen in the hearts and lungs of aged PAD4(−/−) mice compared with wild-type (WT) mice. An increase in left ventricular interstitial collagen deposition and a decline in systolic and diastolic function were present only in WT mice, and not in PAD4(−/−) mice. In an experimental model of cardiac fibrosis, cardiac pressure overload induced NETosis and significant platelet recruitment in WT but not PAD4(−/−) myocardium. DNase 1 was given to assess the effects of extracellular chromatin. PAD4 deficiency or DNase 1 similarly protected hearts from fibrosis. We propose a role for NETs in cardiac fibrosis and conclude that PAD4 regulates age-related organ fibrosis and dysfunction. |
format | Online Article Text |
id | pubmed-5294849 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-52948492017-08-01 Peptidylarginine deiminase 4 promotes age-related organ fibrosis Martinod, Kimberly Witsch, Thilo Erpenbeck, Luise Savchenko, Alexander Hayashi, Hideki Cherpokova, Deya Gallant, Maureen Mauler, Maximilian Cifuni, Stephen M. Wagner, Denisa D. J Exp Med Research Articles Aging promotes inflammation, a process contributing to fibrosis and decline in organ function. The release of neutrophil extracellular traps (NETs [NETosis]), orchestrated by peptidylarginine deiminase 4 (PAD4), damages organs in acute inflammatory models. We determined that NETosis is more prevalent in aged mice and investigated the role of PAD4/NETs in age-related organ fibrosis. Reduction in fibrosis was seen in the hearts and lungs of aged PAD4(−/−) mice compared with wild-type (WT) mice. An increase in left ventricular interstitial collagen deposition and a decline in systolic and diastolic function were present only in WT mice, and not in PAD4(−/−) mice. In an experimental model of cardiac fibrosis, cardiac pressure overload induced NETosis and significant platelet recruitment in WT but not PAD4(−/−) myocardium. DNase 1 was given to assess the effects of extracellular chromatin. PAD4 deficiency or DNase 1 similarly protected hearts from fibrosis. We propose a role for NETs in cardiac fibrosis and conclude that PAD4 regulates age-related organ fibrosis and dysfunction. The Rockefeller University Press 2017-02 /pmc/articles/PMC5294849/ /pubmed/28031479 http://dx.doi.org/10.1084/jem.20160530 Text en © 2017 Martinod et al. https://creativecommons.org/licenses/by-nc-sa/4.0/http://www.rupress.org/terms/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Research Articles Martinod, Kimberly Witsch, Thilo Erpenbeck, Luise Savchenko, Alexander Hayashi, Hideki Cherpokova, Deya Gallant, Maureen Mauler, Maximilian Cifuni, Stephen M. Wagner, Denisa D. Peptidylarginine deiminase 4 promotes age-related organ fibrosis |
title | Peptidylarginine deiminase 4 promotes age-related organ fibrosis |
title_full | Peptidylarginine deiminase 4 promotes age-related organ fibrosis |
title_fullStr | Peptidylarginine deiminase 4 promotes age-related organ fibrosis |
title_full_unstemmed | Peptidylarginine deiminase 4 promotes age-related organ fibrosis |
title_short | Peptidylarginine deiminase 4 promotes age-related organ fibrosis |
title_sort | peptidylarginine deiminase 4 promotes age-related organ fibrosis |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5294849/ https://www.ncbi.nlm.nih.gov/pubmed/28031479 http://dx.doi.org/10.1084/jem.20160530 |
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