title: TGF-beta antisense oligonucleotides modulate expression of matrix metalloproteinases in isolated fibroblasts from radiated skin.
abstract: BACKGROUND
  Transforming growth factor-beta (TGF-beta) has been identified as an important component of wound healing. Recent developments in molecular therapy offer exciting prospects for the modulation of wound healing, specifically those targeting TGF-beta. The purpose of this study was to analyze the effect of TGF-beta targeting on the expression of matrix metalloproteinases (MMPs) in fibroblasts isolated from radiation-induced chronic dermal wounds.
  
  
  METHODS
  The expression of MMPs in tissue samples from radiation-induced chronic dermal wounds was investigated by immunohistochemistry and microarray technique. The effect of TGF-beta targeting using antisense oligonucleotides on the expression of MMPs in isolated fibroblasts was analysed by ELISA and multiplex RT-PCR.
  
  
  RESULTS
  Immunohistochemical investigation and microarray analysis demonstrated an increased expression of MMP protein and mRNA in tissue samples from radiation-induced chronic dermal wounds compared to normal human skin. Antisense TGF-beta oligonucleotide treatment significantly down-regulated MMP secretion in vitro.
  
  
  CONCLUSIONS
  TGF-beta antisense oligonucleotide technology may be a potential therapeutic option for the inhibition of proteolytic tissue destruction in radiation-induced chronic wounds.
authors.affiliation: Department of Hand, Plastic and Reconstructive Surgery, Burn Center, BG-Trauma Center, Plastic and Hand Surgery at University of Heidelberg, Ludwigshafen, Germany. k_riedel1@gmx.de
authors.forename: Katrin
authors.initials: K
authors.lastname: Riedel
authors.forename: T
authors.initials: T
authors.lastname: Kremer
authors.forename: H
authors.initials: H
authors.lastname: Ryssel
authors.forename: F
authors.initials: F
authors.lastname: Riedel
authors.forename: U R
authors.initials: UR
authors.lastname: Goessler
authors.forename: E
authors.initials: E
authors.lastname: Koellensperger
authors.forename: G
authors.initials: G
authors.lastname: Germann
authors.forename: M
authors.initials: M
authors.lastname: Sauerbier
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D002478:Cells, Cultured; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology / Q000528:radiation effects; D019084:Fluorescent Antibody Technique, Indirect; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007124:Immunoenzyme Techniques; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D011832:Radiation Injuries / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D012867:Skin / Q000187:drug effects* / Q000201:enzymology / Q000528:radiation effects; D016212:Transforming Growth Factor beta / Q000235:genetics*; D014945:Wound Healing / Q000187:drug effects* / Q000502:physiology
chemical_list: D015415:Biomarkers; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9