J Korean Soc Plast Reconstr Surg.  2006 Jan;33(1):39-45.

The Effect of the Transcriptional Regulation of Sp1 for TGF-beta1 and CTGF Expression in Scar Formation

• Park DM
• Sohn DG
• Han KH
• Lee SY
• Chae YM
• Chang YC
• Park KK

Abstract

This study is to examine the relationship between TGF-b1 expression and CTGF expression, and to evaluate the effect of Sp1 blockade on the expression of TGF-b1, CTGF and extracellular genes, clones of fibroblasts stably transfected with Sp1 decoy ODN. R-Sp1 decoy ODN was highly resistant to degradation by nucleases or serum, compared to the linear or phosphorothioated-Sp1 decoy ODN. Skin wounds were created on the back of 36 anesthetized rats. They were divided into four groups-the rats with normal skin, with wounded skin without decoy, with wounded skin injected with R-Sp1 decoy, and with wounded skin injected with mismatched R-Sp1 decoy, respectively. Skins were collected at 3rd, 5th, 7th, 14th day after wounding. Cellular RNA was extracted by RT-PCR analysis. TGF-beta1 and CTGF were deeply related with skin fibrosis during scar formation and it appeared that TGF-beta1 may cause the induction of CTGF expression. R-Sp1 decoy ODN inhibited TGF-beta1 and CTGF expression both in cultured fibroblasts and in the skin of rats. These results indicate that targeting Sp1 with R-type decoy efficiently blocks extracellular matrix gene expression, and suggest an important new therapeutic approach to control the scarring in normal wound healing and fibrotic disorders.

Keyword

Scar Formation; Sp1 decoy oligodeoxynucleotide (ODN); Transforming growth factor(TGF)-beta1; Connective tissue growth factor(CTGF)

MeSH Terms

Animals
Cicatrix*
Clone Cells
Extracellular Matrix
Fibroblasts
Fibrosis
Gene Expression
Rats
RNA
Skin
Transforming Growth Factor beta1*
Wound Healing
Wounds and Injuries
RNA
Transforming Growth Factor beta1