UVA irradiation following treatment with topical 8-methoxypsoralen improves bleomycin-induced scleroderma in a mouse model, by reducing the collagen content and collagen gene expression levels in the skin

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• 作者：Shujiro Hayashi^a ; Masashi Ikeda^b ; Yohei Kitamura^a ; Yoichiro Hamasaki^a ; Atsushi Hatamochi^a ; ^{hatamo@dokkyomed.ac.jp}
• 关键词：Systemic sclerosis ; PUVA ; Type I collagen ; TGF-尾1 ; Mouse model of scleroderma ; Bleomycin
• 刊名：Journal of Dermatological Science
• 出版年：2012
• 期刊代码：153_09231811
• 类别：med
• 出版时间：July, 2012
• 卷：67
• 期：1
• 页码：20-25
• 文件大小：1318 K

摘要

Background

Recent studies have demonstrated that systemic or topical PUVA therapy, i.e., ultraviolet A (UVA) irradiation following treatment with 8-methoxypsoralen (8-MOP), is effective against the sclerotic skin lesions in systemic sclerosis. However, the mechanisms still remain unknown.

Objective

To clarify the mechanisms of this therapy, we created a mouse model of bleomycin (BLM) injection-induced scleroderma and evaluated the effects of PUVA on the fibrotic lesions of scleroderma in this mouse model.

Methods

BLM was injected subcutaneously once a day into the mice for 24 days. During the injection period, one group of mice was irradiated with UVA following local application of 8-MOP. Control groups were also set up, which were injected with phosphate-buffered saline, instead of BLM. Skin tissue samples examined histopathologically changes, measured of the content of hydroxyproline, and checked for the expression of genes encoding type I collagen, type III collagen, and transforming growth factor-尾1 (TGF-尾1).

Results

The mouse models of scleroderma was found to show an increase in the density of the collagen fibers and thickening of the dermis and increased expressions of type I collagen, type III collagen, and TGF-尾1. However, the combination of BLM treatment and topical PUVA treatment mice appeared reduced the dermal thickness and hydroxyproline content, down-regulation of expressions of the type I and type III collagen genes was observed while the expression of the TGF-尾1 gene remained unchanged.

Conclusion

These results suggest that the effectiveness of topical PUVA therapy is attributable to the down-regulation of the expressions of the collagen genes by this treatment. The results additionally suggest that is not mediated by down-regulated expression of the TGF-尾1.