Combinatorial omics analysis reveals perturbed lysosomal homeostasis in collagen VII-deficient keratinocytes.

Combinatorial omics analysis reveals perturbed lysosomal homeostasis in collagen VII-deficient keratinocytes. Mol Cell Proteomics. 2018 Jan 11;: Authors: Thriene K, Grüning BA, Bornert O, Erxleben A, Leppert J, Athanasiou I, Weber E, Kiritsi D, Nyström A, Reinheckel T, Backofen R, Has C, Bruckner-Tuderman L, Dengjel J 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 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 colla...
Source: Molecular and Cellular Proteomics : MCP - Category: Molecular Biology Authors: Tags: Mol Cell Proteomics Source Type: research