Disease proteomics reveals modulation of cell microenvironment in recessive dystrophic EB

摘要

Recessive dystrophic epidermolysis bullosa (RDEB), a genetic skin disorder, caused by mutations in the gene encoding collagen VII, a dermal-epidermal adhesion protein, was used as a model for identification of hitherto unknown proteins involved in RDEB pathogenesis by a disease proteomics approach. A strategy using quantitative mass spectrometry (MS), combined with bioinformatics data processing, was developed to assess quantitative differences in the microenvironment of skin fibroblasts derived from normal and pathologically altered skin. This global, unbiased approach revealed unanticipated differences in protein abundance across all examined patient samples, as well as differences observed only for specific patients. The proteomics approach showed that loss of collagen VII was associated with a number of other changes, i.e. decrease of basement membrane proteins and increase of dermal matrix proteins and metalloproteases, but not with higher protease activity. With this resource at hand, we identified novel disease mechanisms in RDEB.