@article{Thriene_Gruning_Bornert-Combi_Omics_Analy-2018,
author = {Thriene, Kerstin and Grüning, Björn Andreas and Bornert, 
          Olivier and Erxleben, Anika and Leppert, Juna and 
          Athanasiou, Ioannis and Weber, Ekkehard and Kiritsi, Dimitra 
          and Nystrom, Alexander and Reinheckel, Thomas and Backofen, 
          Rolf and Has, Cristina and Bruckner-Tuderman, Leena and 
          Dengjel, Jorn},
title = {Combinatorial {Omics} {Analysis} {Reveals} {Perturbed} 
         {Lysosomal} {Homeostasis} in {Collagen} {VII}-deficient 
         {Keratinocytes}},
journal = {Mol Cell Proteomics},
year = {2018},
doi = {10.1074/mcp.RA117.000437},
volume = {17},
user = {backofen},
pmid = {29326176},
pages = {565-579},
number = {4},
issn = {1535-9476},
abstract = {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 from DEB and 
            control subjects 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-beta signaling 
            because of 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.}
}