The mitogen-activated protein kinase p38α regulates tubular damage in murine anti-glomerular basement membrane nephritis.

p38 mitogen-activated protein kinase (MAPK) is thought to play a central role in acute and chronic inflammatory responses. Whether p38MAPK plays a pathogenic role in crescentic GN (GN) and which of its four isoforms is preferentially involved in kidney inflammation is not definitely known. We thus e...

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Autores principales:	Ralf Müller, Christoph Daniel, Christian Hugo, Kerstin Amann, Dirk Mielenz, Karlhans Endlich, Tobias Braun, Betty van der Veen, Peter Heeringa, Georg Schett, Jochen Zwerina
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/55b4f2a8753b4fe3bd95f7f934f33169
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spelling	oai:doaj.org-article:55b4f2a8753b4fe3bd95f7f934f331692021-11-18T07:57:12ZThe mitogen-activated protein kinase p38α regulates tubular damage in murine anti-glomerular basement membrane nephritis.1932-620310.1371/journal.pone.0056316https://doaj.org/article/55b4f2a8753b4fe3bd95f7f934f331692013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23441175/?tool=EBIhttps://doaj.org/toc/1932-6203p38 mitogen-activated protein kinase (MAPK) is thought to play a central role in acute and chronic inflammatory responses. Whether p38MAPK plays a pathogenic role in crescentic GN (GN) and which of its four isoforms is preferentially involved in kidney inflammation is not definitely known. We thus examined expression and activation of p38MAPK isoforms during anti-glomerular basement membrane (GBM) nephritis. Therefore, p38α conditional knockout mice (MxCre-p38α(Δ/Δ)) were used to examine the role of p38α in anti-GBM induced nephritis. Both wild type and MxCre-p38α(Δ/Δ) mice developed acute renal failure over time. Histological examinations revealed a reduced monocyte influx and less tubular damage in MxCre-p38α(Δ/Δ) mice, whereas glomerular crescent formation and renal fibrosis was similar. Likewise, the levels of pro- and anti-inflammatory cytokines such as TNF, IL-1 and IL-10 were similar, but IL-8 was even up-regulated in MxCre-p38α(Δ/Δ) mice. In contrast, we could detect strong down-regulation of chemotactic cytokines such as CCL-2, -5 and -7, in the kidneys of MxCre-p38α(Δ/Δ) mice. In conclusion, p38α is the primary p38MAPK isoform expressed in anti-GBM nephritis and selectively affects inflammatory cell influx and tubular damage. Full protection from nephritis is however not achieved as renal failure and structural damage still occurs.Ralf MüllerChristoph DanielChristian HugoKerstin AmannDirk MielenzKarlhans EndlichTobias BraunBetty van der VeenPeter HeeringaGeorg SchettJochen ZwerinaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 2, p e56316 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ralf Müller Christoph Daniel Christian Hugo Kerstin Amann Dirk Mielenz Karlhans Endlich Tobias Braun Betty van der Veen Peter Heeringa Georg Schett Jochen Zwerina The mitogen-activated protein kinase p38α regulates tubular damage in murine anti-glomerular basement membrane nephritis.
description	p38 mitogen-activated protein kinase (MAPK) is thought to play a central role in acute and chronic inflammatory responses. Whether p38MAPK plays a pathogenic role in crescentic GN (GN) and which of its four isoforms is preferentially involved in kidney inflammation is not definitely known. We thus examined expression and activation of p38MAPK isoforms during anti-glomerular basement membrane (GBM) nephritis. Therefore, p38α conditional knockout mice (MxCre-p38α(Δ/Δ)) were used to examine the role of p38α in anti-GBM induced nephritis. Both wild type and MxCre-p38α(Δ/Δ) mice developed acute renal failure over time. Histological examinations revealed a reduced monocyte influx and less tubular damage in MxCre-p38α(Δ/Δ) mice, whereas glomerular crescent formation and renal fibrosis was similar. Likewise, the levels of pro- and anti-inflammatory cytokines such as TNF, IL-1 and IL-10 were similar, but IL-8 was even up-regulated in MxCre-p38α(Δ/Δ) mice. In contrast, we could detect strong down-regulation of chemotactic cytokines such as CCL-2, -5 and -7, in the kidneys of MxCre-p38α(Δ/Δ) mice. In conclusion, p38α is the primary p38MAPK isoform expressed in anti-GBM nephritis and selectively affects inflammatory cell influx and tubular damage. Full protection from nephritis is however not achieved as renal failure and structural damage still occurs.
format	article
author	Ralf Müller Christoph Daniel Christian Hugo Kerstin Amann Dirk Mielenz Karlhans Endlich Tobias Braun Betty van der Veen Peter Heeringa Georg Schett Jochen Zwerina
author_facet	Ralf Müller Christoph Daniel Christian Hugo Kerstin Amann Dirk Mielenz Karlhans Endlich Tobias Braun Betty van der Veen Peter Heeringa Georg Schett Jochen Zwerina
author_sort	Ralf Müller
title	The mitogen-activated protein kinase p38α regulates tubular damage in murine anti-glomerular basement membrane nephritis.
title_short	The mitogen-activated protein kinase p38α regulates tubular damage in murine anti-glomerular basement membrane nephritis.
title_full	The mitogen-activated protein kinase p38α regulates tubular damage in murine anti-glomerular basement membrane nephritis.
title_fullStr	The mitogen-activated protein kinase p38α regulates tubular damage in murine anti-glomerular basement membrane nephritis.
title_full_unstemmed	The mitogen-activated protein kinase p38α regulates tubular damage in murine anti-glomerular basement membrane nephritis.
title_sort	mitogen-activated protein kinase p38α regulates tubular damage in murine anti-glomerular basement membrane nephritis.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/55b4f2a8753b4fe3bd95f7f934f33169
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The mitogen-activated protein kinase p38α regulates tubular damage in murine anti-glomerular basement membrane nephritis.

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