Journal article
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Combinatorial omics analysis reveals perturbed lysosomal homeostasis in collagen VII-deficient keratinocytes
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Thriene, Kerstin
Department of Dermatology, Medical Center - University of Freiburg, Germany
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Grüning, Björn Andreas
Department of Dermatology, Medical Center - University of Freiburg, Germany
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Bornert, Olivier
Department of Dermatology, Medical Center - University of Freiburg, Germany
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Erxleben, Anika
Department of Dermatology, Medical Center - University of Freiburg, Germany
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Leppert, Juna
Department of Dermatology, Medical Center - University of Freiburg, Germany
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Athanasiou, Ioannis
Department of Dermatology, Medical Center - University of Freiburg, Germany
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Weber, Ekkehard
Centre for Biological Systems Analysis (ZBSA), University of Freiburg, Germany
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Kiritsi, Dimitra
Department of Dermatology, Medical Center - University of Freiburg, Germany
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Nyström, Alexander
Department of Dermatology, Medical Center - University of Freiburg, Germany
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Reinheckel, Thomas
Department of Computer Science, University of Freiburg, Germany
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Backofen, Rolf
Department of Dermatology, Medical Center - University of Freiburg, Germany
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Has, Cristina
Institute of Physiological Chemistry, Medical Faculty, Martin Luther University Halle-Wittenberg, Germany
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Bruckner-Tuderman, Leena
Department of Dermatology, Medical Center - University of Freiburg, Germany
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Dengjel, Jörn
Institute of Molecular Medicine and Cell Research, Faculty of Medicine, University of Freiburg, Germany
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Published in:
- Molecular & Cellular Proteomics. - 2018, vol. 17, no. 4, p. 565-579
English
The extracellular matrix protein collagen VII is part of the microenvironment of stratified epithelia and critical in organismal homeostasis. Mutations in the encoding gene COL7A1 lead to the skin disorder dystrophic epidermolysis bullosa (DEB), are linked to skin fragility and progressive inflammation-driven fibrosis that facilitates aggressive skin cancer. So far, these changes have been linked to mesenchymal alterations, the epithelial consequences of collagen VII loss remaining under- addressed. As epithelial dysfunction is a principal initiator of fibrosis, we performed a comprehensive transcriptome and proteome profiling of primary human keratinocytes to generate global and detailed images of dysregulated epidermal molecular pathways linked to loss of collagen VII. These revealed downregulation of interaction partners of collagen VII on mRNA and protein level, but also increased abundance of S100 pro- inflammatory proteins in primary DEB keratinocytes. Increased TGF-β signaling due to loss of collagen VII was associated with enhanced activity of lysosomal proteases in both keratinocytes and skin of collagen VII-deficient individuals. Thus, loss of a single structural protein, collagen VII, has extra- and intracellular consequences, resulting in inflammatory processes that enable tissue destabilization and promote keratinocyte- driven, progressive fibrosis.
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Faculty
- Faculté des sciences et de médecine
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Department
- Département de Biologie
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Language
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Classification
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Biological sciences
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License
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License undefined
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Identifiers
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Persistent URL
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https://folia.unifr.ch/unifr/documents/306229
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