title: 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.
abstract: 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-β1 (TGF-β1).
  
  
  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-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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Dermatology, Dokkyo Medical University, School of Medicine, Mibu, Tochigi, Japan.
authors.forename: Shujiro
authors.initials: S
authors.lastname: Hayashi
authors.forename: Masashi
authors.initials: M
authors.lastname: Ikeda
authors.forename: Yohei
authors.initials: Y
authors.lastname: Kitamura
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Hamasaki
authors.forename: Atsushi
authors.initials: A
authors.lastname: Hatamochi
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D001761:Bleomycin; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism*; D024061:Collagen Type III / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D015536:Down-Regulation; D005260:Female; D006909:Hydroxyproline / Q000378:metabolism; D008730:Methoxsalen / Q000008:administration & dosage*; D051379:Mice; D008809:Mice, Inbred C3H; D011701:PUVA Therapy; D017319:Photosensitizing Agents / Q000008:administration & dosage*; D012595:Scleroderma, Systemic / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D012867:Skin / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism
chemical_list: D024042:Collagen Type I; D024061:Collagen Type III; D017319:Photosensitizing Agents; C508961:Tgfb1 protein, mouse; D053773:Transforming Growth Factor beta1; D001761:Bleomycin; D006909:Hydroxyproline; D008730:Methoxsalen