The Antimicrobial Peptides Psoriasin (S100A7) and Koebnerisin (S100A15) Suppress Extracellular Matrix Production and Proliferation of Human Fibroblasts
The Antimicrobial Peptides Psoriasin (S100A7) and Koebnerisin (S100A15) Suppress Extracellular Matrix Production and Proliferation of Human Fibroblasts
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DOI：
10.1159/000363579
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发表时间：
2015-01-01
影响因子：
2.7
通讯作者：
Wolf, Ronald
中科院分区：
文献类型：
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作者：
Gauglitz, Gerd G.;Bureik, Daniela;Wolf, Ronald
背景/目的：瘢痕疙瘩是由正常伤口愈合级联的畸变引起的，可导致瘙痒、挛缩和疼痛。过度疤痕的潜在机制尚不清楚，大多数治疗策略仍不令人满意。牛皮癣素（S100A7）和蛇皮素（S100A15）在生理性伤口愈合过程中由角质形成细胞释放。我们发现瘢痕疙瘩组织中S100的产生明显减少。表皮S100表达紊乱可能促进瘢痕疙瘩的形成；因此，我们研究了它们对真皮成纤维细胞和细胞外基质（ECM）产生的影响。方法：采用定量PCR （qPCR）、免疫印迹和免疫荧光染色等方法，分析正常组织和瘢痕疙瘩组织中S100多肽、ECM的调控和分布。分离的真皮成纤维细胞与S100蛋白孵育，采用qPCR检测ECM和转化生长因子(TGF)- β的调控作用。用5-溴-2 '-脱氧尿苷法和结晶紫法测定成纤维细胞的增殖和活力。结果：瘢痕疙瘩组织具有明显的ecm表达，如1型和3型胶原蛋白，而在瘢痕疙瘩来源的细胞和瘢痕疙瘩组织中，银屑病素和koebnerisin的产生明显减少。两种S100蛋白均抑制成纤维细胞胶原、纤维连接蛋白-1、-平滑肌肌动蛋白和tgf - β的表达。此外，它们还能抑制成纤维细胞的增殖。结论：银屑病素和蛇皮素具有抗纤维化作用，可能为纤维增生性疾病的预防和治疗提供新的策略。(C) 2014 S. Karger AG，巴塞尔
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)-beta 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, alpha-smooth-muscle actin and TGF-beta 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. (C) 2014 S. Karger AG, Basel