- September 2019
- 9, suplemento
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- Recessive dystrophic epidermolysis bullosa (RDEB) is a rare skin fragility disorder charac-terized by deficient dermo-epidermal adhesion, due to mutations in the gene encodingcollagen VII. Patients with RDEB suffer chronic wounds and inflammation that ultimatelytrigger fibrosis and highly aggressive squamous cell carcinoma development. We previouslyreported a clinical case of two siblings carrying in homozygosis the same null mutation(c.6527insC) in theCOL7A1gene, but with marked phenotypic differences with respect tothe extent of mucocutaneous involvement, skin fragility and fibrosis. Transcriptomic analysis(RNA-Seq) of primary fibroblasts revealed a significant downregulation in the gene encodingthe antioxidant enzyme ALDH1A1 in all RDEB patients, but not in the sibling with mildphenotype (M-RDEB) whose expression levels remain at those found in fibroblasts fromhealthy volunteers. In this study, flow cytometry analysis showed higher levels of basal andinduced reactive oxygen species (ROS) in RDEB fibroblasts, compared to healthy controls andM-RDEB, suggesting redox imbalance as a possible new disease-severity modulator. Thus,treatment of RDEB fibroblasts with N-acetylcysteine (NAC) as an antioxidant allowed areduction of the fibrotic and activated phenotype, possibly through interaction with the TGF-bpathway. This study proposes a contributing role of oxidative stress in RDEB pathophysiology,opening new therapeutic opportunities to treat the fibrotic and pro-tumorigenic dermalstroma of these patients.