Differential expression of connective tissue growth factor and extracellular matrix proteins in lichen sclerosus

硬化性苔藓中结缔组织生长因子和细胞外基质蛋白的差异表达

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作者:T Gambichler, M Skrygan, V Czempiel, C Tigges, S Kobus, J J Meier, C U Köhler, N Scola, M Stücker, P Altmeyer, A Kreuter

Background

The histopathology of lichen sclerosus (LS) suggests abnormalities in extracellular matrix (ECM) composition. Objectives: We aimed to investigate the expression pattern of ECM proteins and related growths factors and Smad signal transducers in LS as compared with healthy skin.

Conclusions

Expression of ECM proteins (e.g. proteoglycans, ECM-1) and CTGF is altered in LS. TGF-ß/Smad-3 independent up-regulation of CTGF may induce accumulation of ECM proteins and maintain fibrosis in chronic LS.

Methods

To assess the expression of decorin, biglycan, versican, perlecan, fibronectin, dermatopontin, extracellular matrix protein 1 (ECM-1), matrix metalloproteinase 1, tissue inhibitor of metalloproteinase 1, connective tissue growth factor (CTGF), transforming growth factor β1, and Smad-3 protein, real-time RT-PCR and immunohistochemistry were performed on skin specimens obtained from the genital region of healthy subjects (n = 10) as well as LS patients (n = 26).

Results

Median mRNA as well as mean protein expression of biglycan, versican, fibronectin, and ECM-1 was significantly higher in LS when compared with healthy controls. Both mRNA and protein CTGF expression observed in LS was significantly higher than in controls. CTGF mRNA expression significantly correlated with mRNA expression of biglycan, versican and fibronectin. Conclusions: Expression of ECM proteins (e.g. proteoglycans, ECM-1) and CTGF is altered in LS. TGF-ß/Smad-3 independent up-regulation of CTGF may induce accumulation of ECM proteins and maintain fibrosis in chronic LS.

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