title: Down-regulation of miR-223 contributes to the formation of Gottron's papules in dermatomyositis via the induction of PKCɛ.
abstract: BACKGROUND
  Dermatomyositis (DM) is characterized by skin manifestations accompanying and preceding muscle weakness. Gottron's papules, one of the skin manifestations, are of great diagnostic value because they are specific to DM. However, the pathogenesis of Gottron's papules remains unclear.
  
  
  OBJECTIVE
  We investigated the expression pattern of miRNAs in Gottron's papules of DM patients and evaluated the possibility that miRNAs play a role in its pathogenesis.
  
  
  METHODS
  miRNAs were extracted from skin tissues and sera of patients with DM, clinically amyopathic DM (CADM) and healthy controls. To identify pathogenic miRNAs, we performed miRNA PCR array analysis. The results were confirmed by in situ hybridization, immunohistochemistry, immunoblotting and transient transfection of siRNAs or miRNA inhibitors.
  
  
  RESULTS
  PCR array analysis using tissue miRNAs demonstrated the miR-223 level was markedly decreased in Gottron's papules of DM and CADM in vivo, but not in psoriasis skin. The protein expression of PKCɛ, a predicted target of miR-223, was increased in DM/CADM skin. The transfection of a specific inhibitor of miR-223 in keratinocytes led to up-regulation of the PKCɛ protein, and resulted in increased cell proliferation. On the other hand, cell numbers were significantly decreased when cells were transfected with siRNA for PKCɛ. The serum miR-223 concentration was decreased in DM/PM patients, particularly in CADM patients, compared with healthy controls.
  
  
  CONCLUSIONS
  A decreased miR-223 expression and the subsequently increased PKCɛ levels may therefore play a key role in the pathogenesis of Gottron's papules.
authors.affiliation: Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan.
authors.forename: Kuniko
authors.initials: K
authors.lastname: Inoue
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Jinnin
authors.forename: Keitaro
authors.initials: K
authors.lastname: Yamane
authors.forename: Takamitsu
authors.initials: T
authors.lastname: Makino
authors.forename: Ikko
authors.initials: I
authors.lastname: Kajihara
authors.forename: Katsunari
authors.initials: K
authors.lastname: Makino
authors.forename: Norithosi
authors.initials: N
authors.lastname: Honda
authors.forename: Wakana
authors.initials: W
authors.lastname: Nakayama
authors.forename: Satoshi
authors.initials: S
authors.lastname: Fukushima
authors.forename: Hironobu
authors.initials: H
authors.lastname: Ihn
mesh_terms: D049109:Cell Proliferation; D002478:Cells, Cultured; D003882:Dermatomyositis / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D015536:Down-Regulation; D020869:Gene Expression Profiling; D006801:Humans; D015603:Keratinocytes; D035683:MicroRNAs / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D051744:Protein Kinase C-epsilon / Q000378:metabolism*; D034741:RNA, Small Interfering; D014162:Transfection
chemical_list: D035683:MicroRNAs; D051744:Protein Kinase C-epsilon; D034741:RNA, Small Interfering; C525067:MIR223, human
keywords: autoimmune disease; collagen disease; keratinocyte; microRNA; serum