@Article{Thriene_Gruning_Bornert-Combi_Omics_Analy-2018,
  author =	 {Thriene, Kerstin and Gruning, Bjorn 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},
  volume =	 {17},
  number =	 {4},
  pages =	 {565-579},
  user =	 {backofen},
  pmid =	 {29326176},
  doi = 	 {10.1074/mcp.RA117.000437},
  issn = 	 {1535-9476},
  issn = 	 {1535-9484},
  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.}
}