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12R-lipoxygenase deficiency disrupts epidermal barrier function
12R-lipoxygenase (12R-LOX) and the epidermal LOX-3 (eLOX-3) constitute a novel LOX pathway involved in terminal differentiation in skin. This view is supported by recent studies showing that inactivating mutations in 12R-LOX and eLOX-3 are linked to the development of autosomal recessive congenital...
Autores principales: | , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2007
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064121/ https://www.ncbi.nlm.nih.gov/pubmed/17403930 http://dx.doi.org/10.1083/jcb.200612116 |
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author | Epp, Nikolas Fürstenberger, Gerhard Müller, Karsten de Juanes, Silvia Leitges, Michael Hausser, Ingrid Thieme, Florian Liebisch, Gerhard Schmitz, Gerd Krieg, Peter |
author_facet | Epp, Nikolas Fürstenberger, Gerhard Müller, Karsten de Juanes, Silvia Leitges, Michael Hausser, Ingrid Thieme, Florian Liebisch, Gerhard Schmitz, Gerd Krieg, Peter |
author_sort | Epp, Nikolas |
collection | PubMed |
description | 12R-lipoxygenase (12R-LOX) and the epidermal LOX-3 (eLOX-3) constitute a novel LOX pathway involved in terminal differentiation in skin. This view is supported by recent studies showing that inactivating mutations in 12R-LOX and eLOX-3 are linked to the development of autosomal recessive congenital ichthyosis. We show that 12R-LOX deficiency in mice results in a severe impairment of skin barrier function. Loss of barrier function occurs without alterations in proliferation and stratified organization of the keratinocytes, but is associated with ultrastructural anomalies in the upper granular layer, suggesting perturbance of the assembly/extrusion of lamellar bodies. Cornified envelopes from skin of 12R-LOX–deficient mice show increased fragility. Lipid analysis demonstrates a disordered composition of ceramides, in particular a decrease of ester-bound ceramide species. Moreover, processing of profilaggrin to monomeric filaggrin is impaired. This study indicates that the 12R-LOX–eLOX-3 pathway plays a key role in the process of epidermal barrier acquisition by affecting lipid metabolism, as well as protein processing. |
format | Text |
id | pubmed-2064121 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2007 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-20641212007-11-29 12R-lipoxygenase deficiency disrupts epidermal barrier function Epp, Nikolas Fürstenberger, Gerhard Müller, Karsten de Juanes, Silvia Leitges, Michael Hausser, Ingrid Thieme, Florian Liebisch, Gerhard Schmitz, Gerd Krieg, Peter J Cell Biol Research Articles 12R-lipoxygenase (12R-LOX) and the epidermal LOX-3 (eLOX-3) constitute a novel LOX pathway involved in terminal differentiation in skin. This view is supported by recent studies showing that inactivating mutations in 12R-LOX and eLOX-3 are linked to the development of autosomal recessive congenital ichthyosis. We show that 12R-LOX deficiency in mice results in a severe impairment of skin barrier function. Loss of barrier function occurs without alterations in proliferation and stratified organization of the keratinocytes, but is associated with ultrastructural anomalies in the upper granular layer, suggesting perturbance of the assembly/extrusion of lamellar bodies. Cornified envelopes from skin of 12R-LOX–deficient mice show increased fragility. Lipid analysis demonstrates a disordered composition of ceramides, in particular a decrease of ester-bound ceramide species. Moreover, processing of profilaggrin to monomeric filaggrin is impaired. This study indicates that the 12R-LOX–eLOX-3 pathway plays a key role in the process of epidermal barrier acquisition by affecting lipid metabolism, as well as protein processing. The Rockefeller University Press 2007-04-09 /pmc/articles/PMC2064121/ /pubmed/17403930 http://dx.doi.org/10.1083/jcb.200612116 Text en Copyright © 2007, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Research Articles Epp, Nikolas Fürstenberger, Gerhard Müller, Karsten de Juanes, Silvia Leitges, Michael Hausser, Ingrid Thieme, Florian Liebisch, Gerhard Schmitz, Gerd Krieg, Peter 12R-lipoxygenase deficiency disrupts epidermal barrier function |
title | 12R-lipoxygenase deficiency disrupts epidermal barrier function |
title_full | 12R-lipoxygenase deficiency disrupts epidermal barrier function |
title_fullStr | 12R-lipoxygenase deficiency disrupts epidermal barrier function |
title_full_unstemmed | 12R-lipoxygenase deficiency disrupts epidermal barrier function |
title_short | 12R-lipoxygenase deficiency disrupts epidermal barrier function |
title_sort | 12r-lipoxygenase deficiency disrupts epidermal barrier function |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064121/ https://www.ncbi.nlm.nih.gov/pubmed/17403930 http://dx.doi.org/10.1083/jcb.200612116 |
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