title: The role of PSMB9 upregulated by interferon signature in the pathophysiology of cutaneous lesions of dermatomyositis and systemic lupus erythematosus.
abstract: BACKGROUND
  Dermatomyositis (DM) and systemic lupus erythematosus (SLE) have common skin features, including dermal mucin deposition and interferon signature, although their roles are unknown.
  
  
  OBJECTIVE
  To identify common or specific molecular changes in DM and SLE skin.
  
  
  METHODS
  Proteomic analysis was performed using DM and healthy skin. Glycosaminoglycans were analysed by high-performance liquid chromatography.
  
  
  RESULTS
  The expression of 60 proteins was upregulated or downregulated in DM skin compared with healthy skin in the proteomic analysis. Among those proteins, PSMB9, an immunoproteasome subunit, was upregulated in the epidermis of DM and SLE, but not in other skin diseases. Furthermore, versican V1, a core protein for glycosaminoglycans, was upregulated, while type I collagen was downregulated in the dermis of DM and SLE skin. Interferon stimulated PSMB9 expression in cultured keratinocytes and reduced collagen expression in dermal fibroblasts, but did not affect versican expression. The PSMB9 knock-down in keratinocytes led to significant suppression of transforming growth factor (TGF)-β2 and TGF-β3, inducers of versican synthesis. TGF-β3 expression was upregulated in both DM and SLE, while TGF-β2 expression was increased only in the DM epidermis. ΔDiHS-diS1, a component of heparan sulfate, was significantly increased only in DM. TGF-β2 expression significantly increased the ΔDiHS-diS1 expression in dermal fibroblasts in vitro.
  
  
  CONCLUSIONS
  The interferon signature in DM and SLE skin reduces collagen in dermal fibroblasts, whereas overexpression of PSMB9 induced by interferon stimulates versican inducers in epidermal keratinocytes. In addition, the TGF-β2-ΔDiHS-diS1 pathway may be responsible for the specific molecular change in DM skin.
authors.affiliation: Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, 860-8556, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Nakamura
authors.affiliation: Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, 860-8556, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Jinnin
authors.affiliation: Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, 860-8556, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Kudo
authors.affiliation: Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, 860-8556, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Inoue
authors.affiliation: Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, 860-8556, Japan.
authors.forename: W
authors.initials: W
authors.lastname: Nakayama
authors.affiliation: Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, 860-8556, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Honda
authors.affiliation: Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, 860-8556, Japan.
authors.forename: I
authors.initials: I
authors.lastname: Kajihara
authors.affiliation: Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, 860-8556, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Masuguchi
authors.affiliation: Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, 860-8556, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Fukushima
authors.affiliation: Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, 860-8556, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Ihn
mesh_terms: D024042:Collagen Type I / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000502:physiology*; D003879:Dermatologic Agents / Q000494:pharmacology*; D003882:Dermatomyositis / Q000209:etiology* / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D007372:Interferons / Q000494:pharmacology*; D015603:Keratinocytes / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000209:etiology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D040901:Proteomics; D012867:Skin / Q000378:metabolism; D015291:Transforming Growth Factors / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology; D053675:Versicans / Q000378:metabolism
chemical_list: D024042:Collagen Type I; D003879:Dermatologic Agents; D053675:Versicans; C071313:LMP-2 protein; D015291:Transforming Growth Factors; D007372:Interferons; D003546:Cysteine Endopeptidases