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KMID : 0358820060330010039
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Journal of Korean Society of Plastic and Reconstructive Surgeons
2006 Volume.33 No. 1 p.39 ~ p.45
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The Effect of the Transcriptional Regulation of Sp1 for TGF-beta1 and CTGF Expression in Scar Formation
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Park Dong-Man
Son Dae-Gu
Han Ki-Hwan
Lee Sun-Young
Chang Young-Chae
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Abstract
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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.
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KEYWORD
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Scar Fomation, Sp1 decoy oligodeoxynucleotide(ODN), Transforming growth factor(TGF)-b1, Connective tissue growth factor(CTGF)
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