Desmoglein 2 regulates the intestinal epithelial barrier via p38 mitogen-activated protein kinase

Abstract Intestinal epithelial barrier properties are maintained by a junctional complex consisting of tight junctions (TJ), adherens junctions (AJ) and desmosomes. Desmoglein 2 (Dsg2), an adhesion molecule of desmosomes and the only Dsg isoform expressed in enterocytes, is required for epithelial b...

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Autores principales:	Hanna Ungewiß, Franziska Vielmuth, Shintaro T. Suzuki, Andreas Maiser, Hartmann Harz, Heinrich Leonhardt, Daniela Kugelmann, Nicolas Schlegel, Jens Waschke
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e3bf6cdb8c36482bbd4222776e21ef8f
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spelling	oai:doaj.org-article:e3bf6cdb8c36482bbd4222776e21ef8f2021-12-02T16:06:14ZDesmoglein 2 regulates the intestinal epithelial barrier via p38 mitogen-activated protein kinase10.1038/s41598-017-06713-y2045-2322https://doaj.org/article/e3bf6cdb8c36482bbd4222776e21ef8f2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06713-yhttps://doaj.org/toc/2045-2322Abstract Intestinal epithelial barrier properties are maintained by a junctional complex consisting of tight junctions (TJ), adherens junctions (AJ) and desmosomes. Desmoglein 2 (Dsg2), an adhesion molecule of desmosomes and the only Dsg isoform expressed in enterocytes, is required for epithelial barrier properties and may contribute to barrier defects in Crohn’s disease. Here, we identified extradesmosomal Dsg2 on the surface of polarized enterocytes by Triton extraction, confocal microscopy, SIM and STED. Atomic force microscopy (AFM) revealed Dsg2-specific binding events along the cell border on the surface of enterocytes with a mean unbinding force of around 30pN. Binding events were blocked by an inhibitory antibody targeting Dsg2 which under same conditions activated p38MAPK but did not reduce cell cohesion. In enterocytes deficient for Dsg2, p38MAPK activity was reduced and both barrier integrity and reformation were impaired. Dsc2 rescue did not restore p38MAPK activity indicating that Dsg2 is required. Accordingly, direct activation of p38MAPK in Dsg2-deficient cells enhanced barrier reformation demonstrating that Dsg2-mediated activation of p38MAPK is crucial for barrier function. Collectively, our data show that Dsg2, beside its adhesion function, regulates intestinal barrier function via p38MAPK signalling. This is in contrast to keratinocytes and points towards tissue-specific signalling functions of desmosomal cadherins.Hanna UngewißFranziska VielmuthShintaro T. SuzukiAndreas MaiserHartmann HarzHeinrich LeonhardtDaniela KugelmannNicolas SchlegelJens WaschkeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hanna Ungewiß Franziska Vielmuth Shintaro T. Suzuki Andreas Maiser Hartmann Harz Heinrich Leonhardt Daniela Kugelmann Nicolas Schlegel Jens Waschke Desmoglein 2 regulates the intestinal epithelial barrier via p38 mitogen-activated protein kinase
description	Abstract Intestinal epithelial barrier properties are maintained by a junctional complex consisting of tight junctions (TJ), adherens junctions (AJ) and desmosomes. Desmoglein 2 (Dsg2), an adhesion molecule of desmosomes and the only Dsg isoform expressed in enterocytes, is required for epithelial barrier properties and may contribute to barrier defects in Crohn’s disease. Here, we identified extradesmosomal Dsg2 on the surface of polarized enterocytes by Triton extraction, confocal microscopy, SIM and STED. Atomic force microscopy (AFM) revealed Dsg2-specific binding events along the cell border on the surface of enterocytes with a mean unbinding force of around 30pN. Binding events were blocked by an inhibitory antibody targeting Dsg2 which under same conditions activated p38MAPK but did not reduce cell cohesion. In enterocytes deficient for Dsg2, p38MAPK activity was reduced and both barrier integrity and reformation were impaired. Dsc2 rescue did not restore p38MAPK activity indicating that Dsg2 is required. Accordingly, direct activation of p38MAPK in Dsg2-deficient cells enhanced barrier reformation demonstrating that Dsg2-mediated activation of p38MAPK is crucial for barrier function. Collectively, our data show that Dsg2, beside its adhesion function, regulates intestinal barrier function via p38MAPK signalling. This is in contrast to keratinocytes and points towards tissue-specific signalling functions of desmosomal cadherins.
format	article
author	Hanna Ungewiß Franziska Vielmuth Shintaro T. Suzuki Andreas Maiser Hartmann Harz Heinrich Leonhardt Daniela Kugelmann Nicolas Schlegel Jens Waschke
author_facet	Hanna Ungewiß Franziska Vielmuth Shintaro T. Suzuki Andreas Maiser Hartmann Harz Heinrich Leonhardt Daniela Kugelmann Nicolas Schlegel Jens Waschke
author_sort	Hanna Ungewiß
title	Desmoglein 2 regulates the intestinal epithelial barrier via p38 mitogen-activated protein kinase
title_short	Desmoglein 2 regulates the intestinal epithelial barrier via p38 mitogen-activated protein kinase
title_full	Desmoglein 2 regulates the intestinal epithelial barrier via p38 mitogen-activated protein kinase
title_fullStr	Desmoglein 2 regulates the intestinal epithelial barrier via p38 mitogen-activated protein kinase
title_full_unstemmed	Desmoglein 2 regulates the intestinal epithelial barrier via p38 mitogen-activated protein kinase
title_sort	desmoglein 2 regulates the intestinal epithelial barrier via p38 mitogen-activated protein kinase
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/e3bf6cdb8c36482bbd4222776e21ef8f
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Desmoglein 2 regulates the intestinal epithelial barrier via p38 mitogen-activated protein kinase

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