PAR2 absence completely rescues inflammation and ichthyosis caused by altered CAP1/Prss8 expression in mouse skin
| Autor: | Eric Camerer, Stephan Ryser, Friedrich Beermann, Bernadette Breiden, Roch-Philippe Charles, Jean-Christophe Stehle, Konrad Sandhoff, Marek Haftek, Shaun R. Coughlin, Edith Hummler, Martin Steinhoff, Giovanna Crisante, Simona Frateschi, Samuel Rotman, Anne Wilson, Mathieu Membrez, Sarah Rieser |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
skin
Thymic stromal lymphopoietin medicine.medical_treatment Transgene serine protease Prss8 General Physics and Astronomy Inflammation Biology General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences 0302 clinical medicine medicine proteinase-activated receptor-2 epidermal barrier function epithelial sodium-channel netherton-syndrome serine proteases transgenic mice tissue distribution cell-line in-vivo kappa-b 030304 developmental biology transgenic Serine protease 0303 health sciences Multidisciplinary Protease integumentary system Ichthyosis Effector General Chemistry medicine.disease 3. Good health 030220 oncology & carcinogenesis Immunology Cancer research biology.protein Ectopic expression CAP1 ichthyosis medicine.symptom |
| Zdroj: | Nature Communications Nature Communications; Vol 2 Nature Communications, vol. 2, pp. 161 Nature communications |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/ncomms1162 |
| Popis: | 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; Grhl3PAR2/+), 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. The activity of serine proteases, including CAP1/Prss8, is altered in some human skin disorders; however, the downstream effectors of these proteins are relatively unknown. Here, using animal models, the authors show that protease-activated receptor-2 is a critical component of the CAP1/Prss8 signalling cascade. |
| Databáze: | OpenAIRE |
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