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The role of PSMB9 upregulated by interferon signature in the pathophysiology of cutaneous lesions of dermatomyositis and systemic lupus erythematosus.
- Source :
-
The British journal of dermatology [Br J Dermatol] 2016 May; Vol. 174 (5), pp. 1030-41. Date of Electronic Publication: 2016 Mar 25. - Publication Year :
- 2016
-
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.<br />Objectives: To identify common or specific molecular changes in DM and SLE skin.<br />Methods: Proteomic analysis was performed using DM and healthy skin. Glycosaminoglycans were analysed by high-performance liquid chromatography.<br />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.<br />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.<br /> (© 2015 British Association of Dermatologists.)
- Subjects :
- Collagen Type I metabolism
Dermatomyositis metabolism
Female
Gene Expression
Humans
Keratinocytes metabolism
Lupus Erythematosus, Systemic metabolism
Male
Middle Aged
Proteomics
Skin metabolism
Transforming Growth Factors metabolism
Up-Regulation physiology
Versicans metabolism
Cysteine Endopeptidases physiology
Dermatologic Agents pharmacology
Dermatomyositis etiology
Interferons pharmacology
Lupus Erythematosus, Systemic etiology
Subjects
Details
- Language :
- English
- ISSN :
- 1365-2133
- Volume :
- 174
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- The British journal of dermatology
- Publication Type :
- Academic Journal
- Accession number :
- 26713607
- Full Text :
- https://doi.org/10.1111/bjd.14385