title: Down-regulation of microRNA-196a in the sera and involved skin of localized scleroderma patients.
abstract: BACKGROUND
  Localized scleroderma (LSc) exhibits fibrosis of the skin and subcutaneous tissue. LSc shows an excessive deposition of type 1 collagen.
  
  
  OBJECTIVE
  To elucidate the mechanism of type 1 collagen overexpression in LSc, we investigated the epigenetics, focusing on microRNA (miRNA).
  
  
  METHODS
  miRNA expression profile was determined by PCR array analysis. The expression of microRNA-196a (miR-196a) in the skin tissue was examined by in situ hybridization or real-time PCR. The serum levels of miR-196a were measured by real-time PCR.
  
  
  RESULTS
  PCR array analysis demonstrated that the miR-196a level was markedly decreased in LSc skin tissue in vivo. The transfection of specific inhibitor for miR-196a into normal cultured human dermal fibroblasts led to the up-regulation of type 1 collagen protein in vitro. Furthermore, the serum levels of miR-196a were significantly decreased in LSc patients.
  
  
  CONCLUSIONS
  Down-regulation of miR-196a and subsequent overexpression of type 1 collagen in dermal fibroblasts may play a key role in the pathogenesis of LSc. The serum levels of miR-196a may be useful as a diagnostic marker of LSc.
authors.affiliation: Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan.
authors.forename: Takamitsu
authors.initials: T
authors.lastname: Makino
authors.affiliation: Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Jinnin
authors.affiliation: Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan.
authors.forename: Mitsuhiko
authors.initials: M
authors.lastname: Etoh
authors.affiliation: Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan.
authors.forename: Keitaro
authors.initials: K
authors.lastname: Yamane
authors.affiliation: Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan.
authors.forename: Ikko
authors.initials: I
authors.lastname: Kajihara
authors.affiliation: Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan.
authors.forename: Katsunari
authors.initials: K
authors.lastname: Makino
authors.affiliation: Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan.
authors.forename: Asako
authors.initials: A
authors.lastname: Ichihara
authors.affiliation: Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan.
authors.forename: Toshikatsu
authors.initials: T
authors.lastname: Igata
authors.affiliation: Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Sakai
authors.affiliation: Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Fukushima
authors.affiliation: Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Ihn
mesh_terms: D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism; D015536:Down-Regulation; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D035683:MicroRNAs / Q000097:blood / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D012594:Scleroderma, Localized / Q000235:genetics* / Q000378:metabolism*; D012867:Skin / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D024042:Collagen Type I; C542543:MIRN196 microRNA, human; D035683:MicroRNAs
keywords: localized scleroderma; miR-196a; micro RNA; morphea