Control of scarring in adult wounds using antisense transforming growth factor-beta 1 oligodeoxynucleotides.
Adult wounds heal with scar formation, whereas fetal wounds heal without scarring and with a lesser inflammatory and cytokine response. We reasoned that a strategy employing antisense oligodeoxynucleotides (ODN) complementary to transforming growth factor (TGF)-beta-1 mRNA might decrease the scarring of dermal wounds in the mouse. To evaluate this concept, we tested the effects of antisense ODN targeted to TGF-beta 1 mRNA by topical application of the ODN on the skin wound. Phosphorothioation of ODN to retard their degradation. When antisense TGF-beta 1 ODN were applied on the wound site, there was marked reduction of scarring compared with a control wound site. This effect of antisense TGF-beta 1 ODN on scar formation was associated with decreased expression of the TGF-B1 gene. However, sense TGF-beta 1 ODN had no effect on the expression of the TGF-beta 1 gene. In addition, control wounds healed with excessive fibrosis compared with the antisense-treated wounds. In conclusion, our results indicate that antisense TGF-beta 1 ODN could be used for ameliorating scar formation during wound healing.
Choi
B M
BM
Department of Microbiology and Immunology, Wonkwang University School of Medicine, Iksan Chonbuk, Korea.
Kwak
H J
HJ
Jun
C D
CD
Park
S D
SD
Kim
K Y
KY
Kim
H R
HR
Chung
H T
HT
D000818:Animals; D001483:Base Sequence; D002465:Cell Movement; D002478:Cells, Cultured; D002921:Cicatrix / Q000517:prevention & control*; D008264:Macrophages / Q000166:cytology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000627:therapeutic use*; D012867:Skin / Q000293:injuries / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000502:physiology; D014945:Wound Healing; D014947:Wounds and Injuries / Q000188:drug therapy*
D016376:Oligonucleotides, Antisense; D016212:Transforming Growth Factor beta