title: Hepatocyte growth factor-expressing adenovirus upregulates matrix metalloproteinase-1 expression in keloid fibroblasts.
abstract: BACKGROUND
  Keloids are marked by an overabundance of extracellular matrix. The antifibrotic effect of hepatocyte growth factor (HGF) is achieved by increasing the expression of matrix metalloproteinases (MMPs) that drive extracellular matrix catabolism. As such, we cultivated an RGD-modified HGF-expressing adenovirus (dE1-RGD/lacZ/HGF) for introduction into keloid fibroblasts (KFs), looking at the subsequent impact on MMP-1 expression.
  
  
  METHODS
  KFs infected with either test virus as experimental group (dE1-RGD/lacZ/HGF) or its counterpart (dE1-RGD/lacZ) as control group were examined for HGF protein expression using an enzyme-linked immunosorbent assay (ELISA). Collagen (types I and III) and MMP-1 mRNA levels were also determined by reverse transcriptase-polymerase chain reaction, and ELISA was used to monitor MMP-1 protein expression.
  
  
  RESULTS
  In KFs harboring the test virus, high levels of HGF were induced at a multiplicity of infection ratio of 50 (3260.6 ± 162.7 pg/ml) after 72 hours of incubation. Furthermore, reverse transcriptase-polymerase chain reaction and ELISA confirmed that MMP-1 mRNA and protein expression rose significantly in KFs after transduction by the test virus (P < 0.05). However, mRNA levels of collagen were unaffected by the experimental group.
  
  
  CONCLUSIONS
  These results suggest that an HGF-expressing adenovirus may be therapeutic for keloids by increasing MMP-1 expression.
authors.affiliation: Institute for Human Tissue Restoration, Department of Plastic & Reconstructive Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Yeo Reum
authors.initials: YR
authors.lastname: Jeon
authors.affiliation: Department of Bioengineering, College of Engineering, Hanyang University, Seoul, Korea.
authors.forename: Hyo Min
authors.initials: HM
authors.lastname: Ahn
authors.affiliation: Department of Bioengineering, College of Engineering, Hanyang University, Seoul, Korea.
authors.forename: Il Kyu
authors.initials: IK
authors.lastname: Choi
authors.affiliation: Department of Bioengineering, College of Engineering, Hanyang University, Seoul, Korea.
authors.forename: Chae Ok
authors.initials: CO
authors.lastname: Yun
authors.affiliation: Institute for Human Tissue Restoration, Department of Plastic & Reconstructive Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Dong Kyun
authors.initials: DK
authors.lastname: Rah
authors.affiliation: Institute for Human Tissue Restoration, Department of Plastic & Reconstructive Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Dae Hyun
authors.initials: DH
authors.lastname: Lew
authors.affiliation: Institute for Human Tissue Restoration, Department of Plastic & Reconstructive Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Won Jai
authors.initials: WJ
authors.lastname: Lee
mesh_terms: D000256:Adenoviridae; D000328:Adult; D002478:Cells, Cultured; D024042:Collagen Type I / Q000235:genetics; D024043:Collagen Type II / Q000235:genetics; D005260:Female; D005347:Fibroblasts; D005822:Genetic Vectors; D017228:Hepatocyte Growth Factor / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D007627:Keloid / Q000201:enzymology* / Q000235:genetics*; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism*; D061251:Primary Cell Culture; D012333:RNA, Messenger / Q000378:metabolism; D014161:Transduction, Genetic; D015854:Up-Regulation / Q000235:genetics; D055815:Young Adult
chemical_list: D024042:Collagen Type I; D024043:Collagen Type II; D012333:RNA, Messenger; D017228:Hepatocyte Growth Factor; D020781:Matrix Metalloproteinase 1