Low-dose calcipotriol can elicit wound closure, anti-microbial, and anti-neoplastic effects in epidermolysis bullosa keratinocytes

Christina Guttmann-Gruber, Birgit Tockner, Cornelia Scharler, Clemens Hüttner, John E Common, Angeline S L Tay, Simon L I J Denil, Alfred Klausegger, Andrea Trost, Jenny Breitenbach, Peter Schnitzhofer, Peter Hofbauer, Martin Wolkersdorfer, Anja Diem, Martin Laimer, Dirk Strunk, Johann W Bauer, Julia Reichelt, Roland Lang, Josefina Piñón Hofbauer

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Abstrakt

Recessive dystrophic epidermolysis bullosa (RDEB) patients suffer from chronic and repeatedly infected wounds predisposing them to the development of aggressive and life-threatening skin cancer in these areas. Vitamin D3 is an often neglected but critical factor for wound healing. Intact skin possesses the entire enzymatic machinery required to produce active 1-alpha,25-dihydroxyvitamin D3 (calcitriol), underscoring its significance to proper skin function. Injury enhances calcitriol production, inducing the expression of calcitriol target genes including the antimicrobial peptide cathelicidin (hCAP18), an essential component of the innate immune system and an important wound healing factor. We found significantly reduced hCAP18 expression in a subset of RDEB keratinocytes which could be restored by calcipotriol treatment. Reduced scratch closure in RDEB cell monolayers was enhanced up to 2-fold by calcipotriol treatment, and the secretome of calcipotriol-treated cells additionally showed increased antimicrobial activity. Calcipotriol exhibited anti-neoplastic effects, suppressing the clonogenicity and proliferation of RDEB tumor cells. The combined wound healing, anti-microbial, and anti-neoplastic effects indicate that calcipotriol may represent a vital therapeutic option for RDEB patients which we could demonstrate in a single-patient observation study.

OriginalsprogEngelsk
Artikelnummer13430
TidsskriftScientific Reports
Vol/bind8
Udgave nummer1
ISSN2045-2322
DOI
StatusUdgivet - 7. sep. 2018
Udgivet eksterntJa

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