Hepatocyte growth factor-expressing adenovirus upregulates matrix metalloproteinase-1 expression in keloid fibroblasts

Int J Dermatol. 2016 Mar;55(3):356-61. doi: 10.1111/ijd.12965. Epub 2015 Jul 31.

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.

Conclusion: These results suggest that an HGF-expressing adenovirus may be therapeutic for keloids by increasing MMP-1 expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae
  • Adult
  • Cells, Cultured
  • Collagen Type I / genetics
  • Collagen Type II / genetics
  • Female
  • Fibroblasts
  • Genetic Vectors
  • Hepatocyte Growth Factor / genetics*
  • Hepatocyte Growth Factor / metabolism*
  • Humans
  • Keloid / enzymology*
  • Keloid / genetics*
  • Male
  • Matrix Metalloproteinase 1 / genetics
  • Matrix Metalloproteinase 1 / metabolism*
  • Primary Cell Culture
  • RNA, Messenger / metabolism
  • Transduction, Genetic
  • Up-Regulation / genetics
  • Young Adult

Substances

  • Collagen Type I
  • Collagen Type II
  • RNA, Messenger
  • Hepatocyte Growth Factor
  • Matrix Metalloproteinase 1