PROGRAMM JAHRESTAGUNG 2012 30. Nov. – 2. Dez ... - ÖGDV

Poster Wundheilung
P 49
Gene expression studies on the mechanisms of impaired wound healing in
recessive dystrophic epidermolysis bullosa
Jenny Breitenbach 1
Christina Gruber 1
Andrea Trost 2
Barbara Bogner 2
Helmut Hintner 1
Johann Bauer 1
1 SALK/Paracelsus Medical University Salzburg Laboratory for Molecular Therapy, EB
House Austria Department of Dermatology, Muellner Hauptstraße 48,
A-5020 Salzburg
2 SALK/Paracelsus Medical University Salzburg Department of Ophthalmology and
Optometry, Muellner Hauptstraße 48, A-5020 Salzburg
Introduction: In recessive dystrophic epidermolysis bullosa (RDEB), wound healing is
severely impaired with persistent inflammation, chronic wounds, and atrophic scars
caused by repeated friction and infections. Almost all RDEB patients develop
pseudosyndactyly with contractures leading to the loss of finger function, and so far,
there is no treatment that permanently relieves this complication.
Methods and results: Our main goal is to elucidate the mechanisms underlying
scarring and pseudosyndactyly in order to contribute to improving those symptoms
in RDEB. To this end, we performed a genome wide study of gene expression in scarring
and non scarring skin of RDEB patients and healthy persons by cDNA microarrays in
order to identify new genes that are involved in the wound healing process in RDEB
patients. We found numerous genes and functional gene groups with specific differential
regulation in RDEB scars, among them such associated with wound healing,
inflammation, the cytoskeleton, and neuronal function and development. We also
detected a similar gene expression pattern in non scarring skin from RDEB patients and
in scar tissue from healthy donors, indicating permanent increased inflammation and
tissue remodeling in RDEB. Furthermore, we saw that in RDEB patients mostly genes
involved in inflammation, tissue remodeling, and skin development were differentially
regulated. Some of these genes were confirmed by semi-quantitative real time-PCR.
Data mining revealed specific differential regulation of members of the PDGF signaling
pathway in RDEB scars, the TGF-β pathway in scars from healthy persons and RDEB
patients, and the Wnt pathway in scars from healthy persons and RDEB patients and in
non scarring RDEB skin. Since in an RDEB mouse model Fritsch et al. (2008) found
pseudosyndactyly accompanied by accumulation of the fibrosis markers α-SMA and
TN-C in the skin, we also studied the role of those proteins in finger contractures in
human RDEB patients by immuno fluorescence microscopy of tissue from affected
digits. We confirmed strong upregulation of TN-C in RDEB scar skin. However, the
myofibroblast marker α-SMA was not changed.
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