Jenny Breitenbach1, Christina Gruber2, Alfred Klausegger2, Andrea Trost3, Barbara Bogner3, Herbert Reitsamer3, Johann W Bauer2. 1. Cluster Rheumatology, Balneology and Rehabilitation, Vienna, Austria. 2. Research Program for Molecular Therapy of Genodermatoses, EB House Austria, Department of Dermatology, University Hospital of the Paracelsus Medical University, Salzburg, Austria. 3. Department of Ophthalmology and Optometry, Research program for Ophthalmology and Glaucoma Research, Paracelsus Medical University, Salzburg, Austria.
Abstract
BACKGROUND: A genetic blistering skin disease, recessive dystrophic epidermolysis bullosa (RDEB), is marked by severe wound healing defects and finger contractures. The purpose of this investigation was to elucidate the mechanisms of impaired wound healing and pseudosyndactyly occurring in RDEB patients by studying the role of known inflammation and fibrosis markers in RDEB pseudosyndactyly tissue. PATIENTS AND METHODS: We studied the expression of the fibrosis and/or inflammation markers tenascin-C, α-smooth muscle actin, transforming growth factor-β1, interleukin-1β, and interleukin-6 in scarring and nonscarring tissue from healthy donors and RDEB patients by semiquantitative real time-PCR and, where applicable, by immunoblots. Furthermore, the distribution pattern of α-smooth muscle actin and tenascin-C were assessed by immunofluorescence microscopy. RESULTS: Based on mRNA and protein analysis, we found upregulation of tenascin-C, interleukin-1β, and interleukin-6 - but not of transforming growth factor-β1 - in recessive dystrophic epidermolysis bullosa scar samples taken from pseudosyndactyly hands. Unexpectedly, α-smooth muscle actin was not upregulated. CONCLUSIONS: Our results confirm inflammation and fibrosis in recessive dystrophic epidermolysis bullosa, especially in scars, suggesting major roles for these processes in pseudosyndactyly. Our data therefore suggests the potential use of antiinflammatory and antifibrotic drugs in the prevention of pseudosyndactyly.
BACKGROUND: A genetic blistering skin disease, recessive dystrophic epidermolysis bullosa (RDEB), is marked by severe wound healing defects and finger contractures. The purpose of this investigation was to elucidate the mechanisms of impaired wound healing and pseudosyndactyly occurring in RDEBpatients by studying the role of known inflammation and fibrosis markers in RDEB pseudosyndactyly tissue. PATIENTS AND METHODS: We studied the expression of the fibrosis and/or inflammation markers tenascin-C, α-smooth muscle actin, transforming growth factor-β1, interleukin-1β, and interleukin-6 in scarring and nonscarring tissue from healthy donors and RDEBpatients by semiquantitative real time-PCR and, where applicable, by immunoblots. Furthermore, the distribution pattern of α-smooth muscle actin and tenascin-C were assessed by immunofluorescence microscopy. RESULTS: Based on mRNA and protein analysis, we found upregulation of tenascin-C, interleukin-1β, and interleukin-6 - but not of transforming growth factor-β1 - in recessive dystrophic epidermolysis bullosa scar samples taken from pseudosyndactyly hands. Unexpectedly, α-smooth muscle actin was not upregulated. CONCLUSIONS: Our results confirm inflammation and fibrosis in recessive dystrophic epidermolysis bullosa, especially in scars, suggesting major roles for these processes in pseudosyndactyly. Our data therefore suggests the potential use of antiinflammatory and antifibrotic drugs in the prevention of pseudosyndactyly.
Authors: Arkadii K Beilin; Nadezhda A Evtushenko; Daniil K Lukyanov; Nikolay N Murashkin; Eduard T Ambarchian; Alexander A Pushkov; Kirill V Savostyanov; Andrey P Fisenko; Olga S Rogovaya; Andrey V Vasiliev; Ekaterina A Vorotelyak; Nadya G Gurskaya Journal: Int J Mol Sci Date: 2021-02-11 Impact factor: 5.923