Regulatory effects of introduction of an exogenous FGF2 gene on other growth factor genes in a healing tendon

Wound Repair Regen. 2014 Jan-Feb;22(1):111-8. doi: 10.1111/wrr.12129.

Abstract

In this study of a tendon injury model, we investigated how injection of a vector incorporating one growth factor gene changes expression levels of multiple growth factor genes in the healing process. The flexor tendon of chicken toes was completely cut and repaired surgically. The tendons in the experimental arm were injected with an adeno-associated virus-2 vector incorporating basic fibroblast growth-factor gene, whereas the tendons in the control arm were not injected or injected with sham vectors. Using real-time polymerase chain reaction, we found that, within the tendon healing period, a set of growth factor genes-transforming growth factor-β1, vascular endothelial growth factor, and connective tissue growth factor-were significantly up-regulated. Expression of the platelet-derived growth factor-B gene was not changed, and the insulin-like growth factor was down-regulated. A tendon marker gene, scleraxis, was significantly up-regulated in the period. Our study revealed an intriguing finding that introduction of one growth factor gene in the healing tendon modulated expression of multiple growth factor genes. We believe this study may have significant implications in determining the approach of gene therapy, and the findings substantiate that gene therapy using a single growth factor could affect multiple growth factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Avian Proteins / genetics
  • Avian Proteins / metabolism
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Chickens
  • Connective Tissue Growth Factor / genetics
  • Connective Tissue Growth Factor / metabolism
  • Dependovirus / metabolism*
  • Down-Regulation
  • Fibroblast Growth Factor 2 / genetics*
  • Gene Transfer Techniques
  • Genetic Therapy / methods
  • Genetic Vectors
  • Insulin-Like Growth Factor I / genetics
  • Insulin-Like Growth Factor I / metabolism
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Proto-Oncogene Proteins c-sis / genetics
  • Proto-Oncogene Proteins c-sis / metabolism
  • Real-Time Polymerase Chain Reaction
  • Tendon Injuries / pathology*
  • Toes
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism
  • Up-Regulation
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism
  • Wound Healing* / genetics

Substances

  • Avian Proteins
  • Basic Helix-Loop-Helix Transcription Factors
  • Intercellular Signaling Peptides and Proteins
  • Proto-Oncogene Proteins c-sis
  • SCX protein, Gallus gallus
  • Transforming Growth Factor beta
  • Vascular Endothelial Growth Factor A
  • Fibroblast Growth Factor 2
  • Connective Tissue Growth Factor
  • Insulin-Like Growth Factor I