Welcome to the UPF Digital Repository

p38/MKP-1-regulated AKT coordinates macrophage transitions and resolution of inflammation during tissue repair

Show simple item record

dc.contributor.author Perdiguero, Eusebio, 1968-
dc.contributor.author Sousa-Victor, Pedro
dc.contributor.author Ruiz Bonilla, Vanesa, 1979-
dc.contributor.author Jardí, Mercè
dc.contributor.author Caelles Franch, Carme
dc.contributor.author Serrano, Antonio L.
dc.contributor.author Muñoz Cánoves, Pura, 1962-
dc.date.accessioned 2015-12-18T18:27:41Z
dc.date.available 2015-12-18T18:27:41Z
dc.date.issued 2011
dc.identifier.citation Perdiguero E, Sousa-Victor P, Ruiz-Bonilla V, Jardí M, Caelles C, Serrano AL et al. p38/MKP-1-regulated AKT coordinates macrophage transitions and resolution of inflammation during tissue repair. Journal of cell biology. 2011;195(2):307-22. DOI: 10.1083/jcb.201104053
dc.identifier.issn 0021-9525
dc.identifier.uri http://hdl.handle.net/10230/25477
dc.description.abstract 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.
dc.description.sponsorship The authors acknowledge funding from The Ministry of Science and Innovation (PLE2009-0124, SAF2009-09782, FIS-PS09/01267, and SAF2010-21682), Association Française contre les Myopathies, Fundación Marató-TV3/R-Pascual, Muscular Dystrophy Association, and European Union Seventh Framework Programme (Myoage, Optistem, and Endostem). P. Sousa-Victor was supported by a predoctoral fellowship from Fundação para a Ciência e a Tecnologia
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Rockefeller University Press
dc.relation.ispartof Journal of cell biology. 2011;195(2):307-22
dc.rights © Perdiguero et al., 2011. This article is distributed under a Creative Commons License Attribution–Noncommercial–Share Alike 3.0 Unported.
dc.rights.uri http://creativecommons.org/licenses/by-nc-sa/3.0/
dc.subject.other Macròfags
dc.subject.other Inflamació
dc.subject.other Regulació genètica
dc.title p38/MKP-1-regulated AKT coordinates macrophage transitions and resolution of inflammation during tissue repair
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1083/jcb.201104053
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/223576
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/223098
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/241440
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SAF2009-09782
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SAF2010-21682
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/PLE2009-0124
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion

Thumbnail

This item appears in the following Collection(s)

Show simple item record

Search DSpace


Advanced Search

Browse

My Account

Statistics

In collaboration with Compliant to Partaking