The antimicrobial peptides psoriasin (S100A7) and koebnerisin (S100A15) suppress extracellular matrix production and proliferation of human fibroblasts.

نویسندگان

  • Gerd G Gauglitz
  • Daniela Bureik
  • Stephanie Zwicker
  • Thomas Ruzicka
  • Ronald Wolf
چکیده

BACKGROUND/AIMS Keloids result from aberrations in the normal wound healing cascade and can lead to pruritus, contractures and pain. The underlying mechanisms of excessive scarring are not yet understood, and most therapeutic strategies remain unsatisfactory. Psoriasin (S100A7) and koebnerisin (S100A15) are released by keratinocytes during physiological wound healing. We found S100 production is markedly decreased in keloid scar tissue. The disturbed epidermal S100 expression might contribute to keloid formation; thus, we studied their effect on dermal fibroblasts and extracellular matrix (ECM) production. METHODS S100 peptides, ECM regulation and distribution were analysed in normal and keloid tissue by quantitative PCR (qPCR), immunoblotting and immunofluorescent staining. Isolated dermal fibroblasts were incubated with S100 proteins, and the regulation of ECM and transforming growth factor (TGF)-β was determined using qPCR. Fibroblast proliferation and viability were determined by the 5-bromo-2'-deoxyuridine assay and crystal violet assay. RESULTS Keloid tissue featured a pronounced expression of ECMs, such as collagen types 1 and 3, whereas the production of psoriasin and koebnerisin was markedly decreased in keloid-derived cells and keloid tissue. Both S100 proteins inhibited the expression of collagens, fibronectin-1, α-smooth-muscle actin and TGF-β by fibroblasts. Further, they also suppressed fibroblast proliferation. CONCLUSION Psoriasin and koebnerisin show antifibrotic effects and may lead to novel preventive and therapeutic strategies for fibroproliferative diseases.

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عنوان ژورنال:
  • Skin pharmacology and physiology

دوره 28 3  شماره 

صفحات  -

تاریخ انتشار 2015