Korean J Pathol.  2001 Oct;35(5):424-432.

The Effect of Antibody and Gene Therapy for Transforming Growth Factor- 1 on Scar Formation

• Kim JH
• Han KH
• Ahn JD
• Lee IK
• Kim EJ
• Hwang MY
• Park KK

Abstract

BACKGROUND
Transforming growth factor (TGF)- has a large variety of biological functions, including the modulation of inflammation and the immune system, and is presumed to play important roles in repairing wounds and reducing scarring. The objective of this study is to examine the effects of TGF-1 on healing wounds and reducing scarring. We have also analysed the ability of the hemagglutinating virus of Japan (HVJ) liposome mediated antisense oligodeoxynucleotides (ODNs) to specifically inhibit wound-induced expressions of TGF-1 proteins and mRNA in the rat skin.
METHODS
Skin wounds were created on the backs of 80 anesthetized rats. The first group of wounds, as the controls, was unmanipulated. The second group of wounds, as positive controls or an excessive scarring model, was injected with TGF-1 subcutaneously. The third group of wounds was injected with anti-TGF-1 antibody subcutaneously. The fourth group of wounds was injected with HVJ liposome mediated antisense ODNs for TGF-1 subcutaneously. The wounds of all groups were bisected and analysed histologically 5, 10, 15, 30, and 50 days after the wounds were made.
RESULTS
All control wounds (TGF-1 or no injection) healed with scarring, whereas the wounds treated with the antibody or antisense ODNs healed with less scar formation compared to the control group. The wounds treated with the antibody or antisense ODNs had fewer macrophages, less collagen and fibronectin contents than the other wounds. Northern blotting and in situ hybridization analysis showed that wound sites treated with HVJ liposome mediated antisense ODNs for TGF-1 exhibited decreased levels of TGF-1 mRNA after injury.
CONCLUSIONS
These findings suggest an important new approach to controlling scarring in normal wound healing, complementing the practice of adding exogenous growth factors to chronic wounds in the attempt to inhibit collagen deposition.

Keyword

Transforming growth factor beta; Liposomes; Wounds and injuries; Oligoribonucleotides; Antisense

MeSH Terms

Animals
Blotting, Northern
Cicatrix*
Collagen
Complement System Proteins
Fibronectins
Genetic Therapy*
Immune System
In Situ Hybridization
Inflammation
Intercellular Signaling Peptides and Proteins
Liposomes
Macrophages
Oligodeoxyribonucleotides
Oligoribonucleotides
Rats
RNA, Messenger
Sendai virus
Skin
Transforming Growth Factor beta
Transforming Growth Factors
Wound Healing
Wounds and Injuries
Collagen
Complement System Proteins
Fibronectins
Intercellular Signaling Peptides and Proteins
Liposomes
Oligodeoxyribonucleotides
Oligoribonucleotides
RNA, Messenger
Transforming Growth Factor beta
Transforming Growth Factors