Archives of Plastic Surgery

  • 제33권1호
  • /
  • Pages.39-45
  • /
  • 2006
  • /
  • 2234-6163(pISSN)
  • /
  • 2234-6171(eISSN)
대한성형외과학회 (Korean Society of Plastic and Reconstructive Surgeons)
권호 표지

반흔형성 과정에서 Sp1 전사인자 조절에 의한 TGF-β1 및 CTGF의 발현

The Effect of the Transcriptional Regulation of Sp1 for TGF-β1 and CTGF Expression in Scar Formation

  • 박동만 (계명대학교 의학과 성형외과학교실) ;
  • 손대구 (계명대학교 의학과 성형외과학교실) ;
  • 한기환 (계명대학교 의학과 성형외과학교실) ;
  • 이선영 (경북대학교 의과대학 의학연구소) ;
  • 채영미 (대구가톨릭대학교 의과대학 병리학교실) ;
  • 장영채 (대구가톨릭대학교 의과대학 병리학교실) ;
  • 박관규 (대구가톨릭대학교 의과대학 병리학교실)
  • Park, Dong Man (Department of Plastic and Reconstructive Surgery, Keimyung University School of Medicine) ;
  • Sohn, Dae Gu (Department of Plastic and Reconstructive Surgery, Keimyung University School of Medicine) ;
  • Han, Ki Hwan (Department of Plastic and Reconstructive Surgery, Keimyung University School of Medicine) ;
  • Lee, Sun Young (Department of Medical Research Institute, Kyungpook National University) ;
  • Chae, Young Mi (Department of Pathology, College of Medicine, Catholic University of Daegu) ;
  • Chang, Young Chae (Department of Pathology, College of Medicine, Catholic University of Daegu) ;
  • Park, Kwan Kyu (Department of Pathology, College of Medicine, Catholic University of Daegu)
  • 투고 : 2005.08.31
  • 발행 : 2006.01.10
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

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-${\beta}1$ and CTGF were deeply related with skin fibrosis during scar formation and it appeared that TGF-${\beta}1$ may cause the induction of CTGF expression. R-Sp1 decoy ODN inhibited TGF-${\beta}1$ 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.

키워드

참고문헌

  1. Diaz BV, Lenoir Me Ladoux A Frelin c. Demarchez M, Michel S: Regulation of vascular endothelial growth factor expression in human keratinocytes by retinoids. J Bioi Chem 275: 642, 2000 https://doi.org/10.1074/jbc.275.1.642
  2. Mann MJ, Dzau VJ: Therapeutic applications of transcription factor decoy oligonucleotides. J Clin Invest 106: 1071, 2000 https://doi.org/10.1172/JCI11459
  3. Shinozaki M, Kawara S, Hayashi N, Kakinuma T, Igarashi A Takehara K Induction of subcutaneous tissue fibrosis in newborn mice by transforming growth factor-B:Simultaneous application with basic fibroblast growth factor causes persistent fibrosis. Biochem Biophys Res Commun 240, 292, 1997
  4. Peltonen J, Kahari L, Jaakkola S, Kahari VM, Varga J, Ditto J, Jimenez SA: Evaluation of transforming growth factor beta and type I procollagen gene expression in fibrotic skin diseases by in situ hybridization. J Invest Dennatol 94: 365, 1990 https://doi.org/10.1111/1523-1747.ep12874491
  5. Cox DA, Maurer T: Transforming growth factor-B. Clin Immunol Immunopathol 83: 25, 1997 https://doi.org/10.1006/clin.1996.4308
  6. Assoian RK, Fleurdelys BE, Stevenson HC, Miller PJ, Madtes DK, Raines EW, Ross R, Sporn MB: Expression and secretion of type beta transforming growth factor by activated human macrophages. Proc Natl Acad Sci USA 84: 6020, 1987
  7. Igarashi A, Nashiro K, Kikuchi K, Sato S, Ihn H, Fujimoto M, Grotendorst GR, Takehara K: Connective tissue growth factor gene expression in tissue sections from localized scleroderma, keloid, and other fibrotic skin disease. J Invest Dermatol 106: 729, 1996 https://doi.org/10.1111/1523-1747.ep12345771
  8. Bielinska A, Shivdasani RA, Zhang LQ Nabel GJ:Regulation of gene expression with double-stranded phosphorothioate oligonucleotides. Science 250: 997, 1990 https://doi.org/10.1126/science.2237444
  9. Geiser AG, Busam KJ, Kim SJ, Lafyatis R, O'Reilly MA, Webbink R, Roberts AB, Sporn MB: Regulation of the transforming growth factor-beta 1 and -beta 3 promoters by transcription factor Sp1. Gene 129: 223, 1993 https://doi.org/10.1016/0378-1119(93)90272-5
  10. Quaglino 0 Jr, Nanney LB, Ditesheim JA, Davidson JM:Transforming growth factor-beta stimulates wound healing and modulates extracellular matrix gene expression in pig skin: Incisional wound model. J Invest Dermaiol 97: 34, 1991
  11. Yamashita J, Yoshimasa T, Arai H, Hiraoka J, Tayaya K, Miyamoto Y, Ogawa Y, Itoh H, Nakao K: Identification of cis-elements of the human endothelin-A receptor gene and inhibition of the gene expression by the decoy strategy. J Bioi Chem 273: 15993, 1998 https://doi.org/10.1074/jbc.273.26.15993
  12. Verrecchia F, Rossert J, Mauviel A: Blocking sp1 transcription factor broadly inhibits extracellular matrix gene expression in vitro and in vivo: Implications for the treatment of tissue fibrosis. J Invest Dermatol 116: 755, 2001 https://doi.org/10.1046/j.1523-1747.2001.01326.x
  13. Morishita R Gibbons GH, Horiuchi M, Ellison KE, Nakama M, Zhang L, Kaneda Y, Ogihara T, Dzau VJ: A gene therapy strategy using a transcription factor decoy of the E2F binding site inhibits smooth muscle proliferation in vivo. Proc Natl Acad Sci USA 92: 5855, 1995
  14. Poncelet AC, Schnaper HW: Sp1 and Smad proteins cooperate to mediate transforming growth factor-b1-induced 31(1) collagen expression in human glomerular mesangial cells. J Bioi Chem 276: 6983, 2001 https://doi.org/10.1074/jbc.M006442200
  15. Kim Y, Ratziu V, Choi SG, Lalazar A, Theiss G, Dang Q Kim SJ, Friedman SL: Transcriptional activation of transforming growth factor b1 and its receptors by the kruppel-like Factor Zi9/core promoter-binding protein and Sp1: Potential mechanisms for autocrine fibrogenesis in response to injury. J Bioi Chem 273: 33750, 1998 https://doi.org/10.1074/jbc.273.50.33750