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p38/MKP-1–regulated AKT coordinates macrophage transitions and resolution of inflammation during tissue repair
Repair of damaged tissue requires the coordinated action of inflammatory and tissue-specific cells to restore homeostasis, but the underlying regulatory mechanisms are poorly understood. In this paper, we report new roles for MKP-1 (mitogen-activated protein kinase [MAPK] phosphatase-1) in controlli...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3198158/ https://www.ncbi.nlm.nih.gov/pubmed/21987635 http://dx.doi.org/10.1083/jcb.201104053 |
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author | Perdiguero, Eusebio Sousa-Victor, Pedro Ruiz-Bonilla, Vanessa Jardí, Mercè Caelles, Carme Serrano, Antonio L. Muñoz-Cánoves, Pura |
author_facet | Perdiguero, Eusebio Sousa-Victor, Pedro Ruiz-Bonilla, Vanessa Jardí, Mercè Caelles, Carme Serrano, Antonio L. Muñoz-Cánoves, Pura |
author_sort | Perdiguero, Eusebio |
collection | PubMed |
description | Repair of damaged tissue requires the coordinated action of inflammatory and tissue-specific cells to restore homeostasis, but the underlying regulatory mechanisms are poorly understood. In this paper, we report new roles for MKP-1 (mitogen-activated protein kinase [MAPK] phosphatase-1) in controlling macrophage phenotypic transitions necessary for appropriate muscle stem cell–dependent tissue repair. By restricting p38 MAPK activation, MKP-1 allows the early pro- to antiinflammatory macrophage transition and the later progression into a macrophage exhaustion-like state characterized by cytokine silencing, thereby permitting resolution of inflammation as tissue fully recovers. p38 hyperactivation in macrophages lacking MKP-1 induced the expression of microRNA-21 (miR-21), which in turn reduced PTEN (phosphatase and tensin homologue) levels, thereby extending AKT activation. In the absence of MKP-1, p38-induced AKT activity anticipated the acquisition of the antiinflammatory gene program and final cytokine silencing in macrophages, resulting in impaired tissue healing. Such defects were reversed by temporally controlled p38 inhibition. Conversely, miR-21–AKT interference altered homeostasis during tissue repair. This novel regulatory mechanism involving the appropriate balance of p38, MKP-1, miR-21, and AKT activities may have implications in chronic inflammatory degenerative diseases. |
format | Online Article Text |
id | pubmed-3198158 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-31981582012-04-17 p38/MKP-1–regulated AKT coordinates macrophage transitions and resolution of inflammation during tissue repair Perdiguero, Eusebio Sousa-Victor, Pedro Ruiz-Bonilla, Vanessa Jardí, Mercè Caelles, Carme Serrano, Antonio L. Muñoz-Cánoves, Pura J Cell Biol Research Articles Repair of damaged tissue requires the coordinated action of inflammatory and tissue-specific cells to restore homeostasis, but the underlying regulatory mechanisms are poorly understood. In this paper, we report new roles for MKP-1 (mitogen-activated protein kinase [MAPK] phosphatase-1) in controlling macrophage phenotypic transitions necessary for appropriate muscle stem cell–dependent tissue repair. By restricting p38 MAPK activation, MKP-1 allows the early pro- to antiinflammatory macrophage transition and the later progression into a macrophage exhaustion-like state characterized by cytokine silencing, thereby permitting resolution of inflammation as tissue fully recovers. p38 hyperactivation in macrophages lacking MKP-1 induced the expression of microRNA-21 (miR-21), which in turn reduced PTEN (phosphatase and tensin homologue) levels, thereby extending AKT activation. In the absence of MKP-1, p38-induced AKT activity anticipated the acquisition of the antiinflammatory gene program and final cytokine silencing in macrophages, resulting in impaired tissue healing. Such defects were reversed by temporally controlled p38 inhibition. Conversely, miR-21–AKT interference altered homeostasis during tissue repair. This novel regulatory mechanism involving the appropriate balance of p38, MKP-1, miR-21, and AKT activities may have implications in chronic inflammatory degenerative diseases. The Rockefeller University Press 2011-10-17 /pmc/articles/PMC3198158/ /pubmed/21987635 http://dx.doi.org/10.1083/jcb.201104053 Text en © 2011 Perdiguero et al. 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 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Research Articles Perdiguero, Eusebio Sousa-Victor, Pedro Ruiz-Bonilla, Vanessa Jardí, Mercè Caelles, Carme Serrano, Antonio L. Muñoz-Cánoves, Pura p38/MKP-1–regulated AKT coordinates macrophage transitions and resolution of inflammation during tissue repair |
title | p38/MKP-1–regulated AKT coordinates macrophage transitions and resolution of inflammation during tissue repair |
title_full | p38/MKP-1–regulated AKT coordinates macrophage transitions and resolution of inflammation during tissue repair |
title_fullStr | p38/MKP-1–regulated AKT coordinates macrophage transitions and resolution of inflammation during tissue repair |
title_full_unstemmed | p38/MKP-1–regulated AKT coordinates macrophage transitions and resolution of inflammation during tissue repair |
title_short | p38/MKP-1–regulated AKT coordinates macrophage transitions and resolution of inflammation during tissue repair |
title_sort | p38/mkp-1–regulated akt coordinates macrophage transitions and resolution of inflammation during tissue repair |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3198158/ https://www.ncbi.nlm.nih.gov/pubmed/21987635 http://dx.doi.org/10.1083/jcb.201104053 |
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