Extracellular Matrix Signature of Dystrophic Epidermolysis Bullosa Patients Skin Cells

Extracellular matrix (ECM), although long viewed to have a primordial structural function, has a vital role in overall tissue homeostasis and disease. Dystrophic epidermolysis bullosa (DEB) is a genetic skin disease caused by gene mutations on COL7A1. As a consequence, these patients’ skin has compromised resistance against friction resulting in constant skin blistering and serious chronic wounds. To date, the existent information on the consequences of the COL7A1 mutations over the ECM is very scarce. Hence, this work aims to unravel the alterations in the ECM produced by fibroblasts from DEB patients in comparison with healthy individuals. For that purpose, healthy primary fibroblasts and immortalized cell lines of three different variants of DEB, provided by EB house Austria, were cultured for 14 days with ascorbic acid to maximize ECM deposition. Gene expression analysis showed that mutations in COL7A1 lead to a downregulation of both collagen VII and I – important ECM players in skin homeostasis. Additionally, analysis of protein expression showed a reduction in basement membrane proteins, such as collagen IV and laminin, together with an increase in dermal matrix proteins greatly associated with wound healing and scarring, namely tenascin C and vimentin. Our preliminary results pointed out that the impaired function of collagen VII impacts ECM composition of important proteins that are closely altered in the diseased scenario.

Acknowledgements:The authors would like to acknowledge FCT for grant SFRH/BD/137766/2018 (MDM) and contract CEECIND/00695/2017 (MTC),the ERC Consolidator Grant – ECM_INK (ERC-2016-COG-726061),the European Union for The Discoveries Centre for Regenerative and Precision Medicine (H2020-WIDESPREAD-2014-1-739572)