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

Abstract:

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.

journal_name

Skin Pharmacol Physiol

authors

Gauglitz GG,Bureik D,Zwicker S,Ruzicka T,Wolf R

doi

10.1159/000363579

subject

Has Abstract

pub_date

2015-01-01 00:00:00

pages

115-23

issue

3

eissn

1660-5527

issn

1660-5535

pii

000363579

journal_volume

28

pub_type

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