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

• DOI: 10.1016/j.jdermsci.2012.02.013
• Publication Date: 2012-03-16T22:52:17Z
• Authors: Shujiro Hayashi; Masashi Ikeda; Yohei Kitamura; Yoichiro Hamasaki; Atsushi Hatamochi
• Keywords: 0301 basic medicine; Mice, Inbred C3H; Photosensitizing Agents; Scleroderma, Systemic; Down-Regulation; Administration, Cutaneous; Collagen Type I; 3. Good health; Transforming Growth Factor beta1; Bleomycin; Disease Models, Animal; Hydroxyproline; Mice; 03 medical and health sciences; Collagen Type III; Animals; Methoxsalen; Female; PUVA Therapy; Skin

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.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.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-β1 (TGF-β1).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-β1. 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-β1 gene remained unchanged.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-β1.