title: Alteration of circulating miRNAs in SSc: miR-30b regulates the expression of PDGF receptor β.
abstract: OBJECTIVE
  Although several miRNAs have been shown to regulate autoimmune pathogenesis by affecting lymphocyte function, the roles of miRNAs in the pathogenesis of SSc remain unclear. Therefore the purpose of this study was to identify miRNAs that play a role in the pathogenesis of SSc by quantitative PCR screening of serum miRNAs.
  
  
  METHODS
  Ninety-five miRNAs that were predicted to target SSc-related genes [IL-4, TGF-β, CTGF, PDGF-B, PDGF receptor (PDGFR) α/β and COL1A2) by in silico analyses were selected. The expression of these miRNAs in sera of SSc patients and healthy controls was measured by quantitative PCR. Involvement of miR-30b, which was most strongly down-regulated in SSc patients, in the regulation of PDGFR-β expression was examined by transfection experiments and 3'-untranslated region (3'-UTR) target luciferase assays. The expression of miR-30b in skin was evaluated in a bleomycin-induced dermal fibrosis model in mice and in SSc patients.
  
  
  RESULTS
  Nineteen of 95 miRNAs were significantly decreased in the sera of SSc patients. Among them, miR-30b was most strongly down-regulated in SSc patients (P = 0.00006) and the levels of miR-30b were inversely correlated with modified Rodnan skin scores. Transfection of a miR-30b mimic repressed PDGFR-β expression in dermal fibroblasts and the activity of a luciferase reporter containing 3'-UTR of PDGFR-β. Moreover, the expression of miR-30b was down-regulated in bleomycin-treated sclerotic skin and in affected skin in SSc patients.
  
  
  CONCLUSIONS
  Down-regulation of miR-30b might be involved in the pathogenesis of SSc.
authors.affiliation: Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chiba City, Chiba 260-8670, Japan. suaki@faculty.chiba-u.jp.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Tanaka
authors.forename: Akira
authors.initials: A
authors.lastname: Suto
authors.forename: Kei
authors.initials: K
authors.lastname: Ikeda
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Sanayama
authors.forename: Daiki
authors.initials: D
authors.lastname: Nakagomi
authors.forename: Taro
authors.initials: T
authors.lastname: Iwamoto
authors.forename: Kotaro
authors.initials: K
authors.lastname: Suzuki
authors.forename: Naotomo
authors.initials: N
authors.lastname: Kambe
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Matsue
authors.forename: Ryutaro
authors.initials: R
authors.lastname: Matsumura
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kashiwakuma
authors.forename: Itsuo
authors.initials: I
authors.lastname: Iwamoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakajima
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001761:Bleomycin; D016022:Case-Control Studies; D002478:Cells, Cultured; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000096:biosynthesis / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics; D045743:Scleroderma, Diffuse / Q000235:genetics / Q000378:metabolism; D045745:Scleroderma, Limited / Q000235:genetics / Q000378:metabolism; D012595:Scleroderma, Systemic / Q000235:genetics* / Q000378:metabolism; D012598:Sclerosis; D012867:Skin / Q000378:metabolism / Q000473:pathology; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000494:pharmacology
chemical_list: C546086:MIRN30b microRNA, human; D035683:MicroRNAs; D016212:Transforming Growth Factor beta; D001761:Bleomycin; D020797:Receptor, Platelet-Derived Growth Factor beta
keywords: PDGF receptor β; SSc; miR-30b; miRNA