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PAR2 absence completely rescues inflammation and ichthyosis caused by altered CAP1/Prss8 expression in mouse skin
Altered serine protease activity is associated with skin disorders in humans and in mice. The serine protease channel-activating protease-1 (CAP1; also termed protease serine S1 family member 8 (Prss8)) is important for epidermal homeostasis and is thus indispensable for postnatal survival in mice,...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3105307/ https://www.ncbi.nlm.nih.gov/pubmed/21245842 http://dx.doi.org/10.1038/ncomms1162 |
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author | Frateschi, Simona Camerer, Eric Crisante, Giovanna Rieser, Sarah Membrez, Mathieu Charles, Roch-Philippe Beermann, Friedrich Stehle, Jean-Christophe Breiden, Bernadette Sandhoff, Konrad Rotman, Samuel Haftek, Marek Wilson, Anne Ryser, Stephan Steinhoff, Martin Coughlin, Shaun R. Hummler, Edith |
author_facet | Frateschi, Simona Camerer, Eric Crisante, Giovanna Rieser, Sarah Membrez, Mathieu Charles, Roch-Philippe Beermann, Friedrich Stehle, Jean-Christophe Breiden, Bernadette Sandhoff, Konrad Rotman, Samuel Haftek, Marek Wilson, Anne Ryser, Stephan Steinhoff, Martin Coughlin, Shaun R. Hummler, Edith |
author_sort | Frateschi, Simona |
collection | PubMed |
description | Altered serine protease activity is associated with skin disorders in humans and in mice. The serine protease channel-activating protease-1 (CAP1; also termed protease serine S1 family member 8 (Prss8)) is important for epidermal homeostasis and is thus indispensable for postnatal survival in mice, but its roles and effectors in skin pathology are poorly defined. In this paper, we report that transgenic expression in mouse skin of either CAP1/Prss8 (K14-CAP1/Prss8) or protease-activated receptor-2 (PAR2; Grhl3(PAR2/+)), one candidate downstream target, causes epidermal hyperplasia, ichthyosis and itching. K14-CAP1/Prss8 ectopic expression impairs epidermal barrier function and causes skin inflammation characterized by an increase in thymic stromal lymphopoietin levels and immune cell infiltrations. Strikingly, both gross and functional K14-CAP1/Prss8-induced phenotypes are completely negated when superimposed on a PAR2-null background, establishing PAR2 as a pivotal mediator of pathogenesis. Our data provide genetic evidence for PAR2 as a downstream effector of CAP1/Prss8 in a signalling cascade that may provide novel therapeutic targets for ichthyoses, pruritus and inflammatory skin diseases. |
format | Text |
id | pubmed-3105307 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-31053072011-06-01 PAR2 absence completely rescues inflammation and ichthyosis caused by altered CAP1/Prss8 expression in mouse skin Frateschi, Simona Camerer, Eric Crisante, Giovanna Rieser, Sarah Membrez, Mathieu Charles, Roch-Philippe Beermann, Friedrich Stehle, Jean-Christophe Breiden, Bernadette Sandhoff, Konrad Rotman, Samuel Haftek, Marek Wilson, Anne Ryser, Stephan Steinhoff, Martin Coughlin, Shaun R. Hummler, Edith Nat Commun Article Altered serine protease activity is associated with skin disorders in humans and in mice. The serine protease channel-activating protease-1 (CAP1; also termed protease serine S1 family member 8 (Prss8)) is important for epidermal homeostasis and is thus indispensable for postnatal survival in mice, but its roles and effectors in skin pathology are poorly defined. In this paper, we report that transgenic expression in mouse skin of either CAP1/Prss8 (K14-CAP1/Prss8) or protease-activated receptor-2 (PAR2; Grhl3(PAR2/+)), one candidate downstream target, causes epidermal hyperplasia, ichthyosis and itching. K14-CAP1/Prss8 ectopic expression impairs epidermal barrier function and causes skin inflammation characterized by an increase in thymic stromal lymphopoietin levels and immune cell infiltrations. Strikingly, both gross and functional K14-CAP1/Prss8-induced phenotypes are completely negated when superimposed on a PAR2-null background, establishing PAR2 as a pivotal mediator of pathogenesis. Our data provide genetic evidence for PAR2 as a downstream effector of CAP1/Prss8 in a signalling cascade that may provide novel therapeutic targets for ichthyoses, pruritus and inflammatory skin diseases. Nature Publishing Group 2011-01-18 /pmc/articles/PMC3105307/ /pubmed/21245842 http://dx.doi.org/10.1038/ncomms1162 Text en Copyright © 2011, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by-nc-nd/3.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/ |
spellingShingle | Article Frateschi, Simona Camerer, Eric Crisante, Giovanna Rieser, Sarah Membrez, Mathieu Charles, Roch-Philippe Beermann, Friedrich Stehle, Jean-Christophe Breiden, Bernadette Sandhoff, Konrad Rotman, Samuel Haftek, Marek Wilson, Anne Ryser, Stephan Steinhoff, Martin Coughlin, Shaun R. Hummler, Edith PAR2 absence completely rescues inflammation and ichthyosis caused by altered CAP1/Prss8 expression in mouse skin |
title | PAR2 absence completely rescues inflammation and ichthyosis caused by altered CAP1/Prss8 expression in mouse skin |
title_full | PAR2 absence completely rescues inflammation and ichthyosis caused by altered CAP1/Prss8 expression in mouse skin |
title_fullStr | PAR2 absence completely rescues inflammation and ichthyosis caused by altered CAP1/Prss8 expression in mouse skin |
title_full_unstemmed | PAR2 absence completely rescues inflammation and ichthyosis caused by altered CAP1/Prss8 expression in mouse skin |
title_short | PAR2 absence completely rescues inflammation and ichthyosis caused by altered CAP1/Prss8 expression in mouse skin |
title_sort | par2 absence completely rescues inflammation and ichthyosis caused by altered cap1/prss8 expression in mouse skin |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3105307/ https://www.ncbi.nlm.nih.gov/pubmed/21245842 http://dx.doi.org/10.1038/ncomms1162 |
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