Oncostatin M이 피부섬유모세포의 증식과 기질생성에 미치는 영향

Effect of Oncostatin M on Proliferation and Matrix Synthesis of Dermal Fibroblasts

  • 전경욱 (단국대학교 의과대학 성형외과학교실) ;
  • 임형우 (고려대학교 의과대학 성형외과학교실) ;
  • 한승규 (고려대학교 의과대학 성형외과학교실) ;
  • 김우경 (고려대학교 의과대학 성형외과학교실)
  • Chun, Kyung Wook (Department of Plastic Surgery, Dankook University) ;
  • Lim, Hyung Woo (Department of Plastic Surgery, Korea University College of Medicine) ;
  • Han, Seung-Kyu (Department of Plastic Surgery, Korea University College of Medicine) ;
  • Kim, Woo Kyung (Department of Plastic Surgery, Korea University College of Medicine)
  • 투고 : 2007.11.23
  • 발행 : 2008.03.10

초록

Purpose: Oncostatin M(OSM) is a multifunctional cytokine that belongs to the interleukin(IL)-6 family. Although there have been a number of studies that focused on the role and mechanism of OSM in various organs and tissues, there are few reports on its effect on wound healing. The final purpose of this project is to evaluate the effect of OSM on wound healing. This pilot study was designed to investigate the effect of OSM on proliferation and matrix synthesis of human dermal fibroblasts, which are the major components of the wound healing. Methods: Excess skin that was obtained from patients who underwent skin grafts, was used for this study. From this material, fibroblasts were isolated and cultured. The cultured fibroblasts were treated with one of four concentrations of OSM. The OSM concentrations used were 0, 50, 100, and 200 ng/ml, respectively. After the OSM treatment, cell proliferation was determined by the MTT assay, collagen synthesis by the C1CP method, GAG levels by the Blyscan Dye method. The parameter levels of each group were compared. Results: OSM treatment increased all the components tested in the study. In particular, cell proliferation, GAG synthesis demonstrated statistically significant increases(p<0.05 in the Mann-Whitney U-test). The highest increase in all the components was obtained at a 100 ng/ml concentration of OSM.Conclusion: The results of the present study indicate that OSM stimulates proliferation and matrix synthesis of human dermal fibroblast and the optimal concentration for wound healing is 100 ng/mL.

키워드

참고문헌

  1. Hibi M, Nakajima K, Hirano T: IL-6 cytokine family and signal transduction: a model of the cytokine system. J Mol Med 74: 1, 1996 https://doi.org/10.1007/BF00202068
  2. Brown TJ, Lioubin MN, Marquardt H: Purification and characterization of cytostatic lymphokines produced by activated human T lymphocytes. Synergistic antiproliferative activity of transforming growth factor beta 1, interferon-gamma, and oncostatin M for human melanoma cells. J Immunol 139: 2977, 1987
  3. Scaffidi AK, Mutsaers SE, Moodley YP, McAnulty RJ, Laurent GJ, Thompson PJ, Knight DA: Oncostatin M stimulates proliferation, induces collagen production and inhibits apoptosis of human lung fibroblasts. Br J Pharmacol 136: 793, 2002 https://doi.org/10.1038/sj.bjp.0704769
  4. Mosley B, De Imus C, Friend D, Boiani N, Thoma B, Park LS, Cosman D: Dual oncostatin M(OSM) receptors. Cloning and characterization of an alternative signaling subunit conferring OSM-specific receptor activation. J Biol Chem 271: 32635, 1996 https://doi.org/10.1074/jbc.271.51.32635
  5. Richards CD, Shoyab M, Brown TJ, Gauldie J: Selective regulation of metalloproteinase inhibitor(TIMP-1) by oncostatin M in fibroblasts in culture. J Immunol 150: 5596, 1993
  6. Bamber B, Reife RA, Haugen HS, Clegg CH: Oncostatin M stimulates excessive extracellular matrix accumulation in a transgenic mouse model of connective tissue disease. J Mol Med 76: 61, 1998 https://doi.org/10.1007/s109-1998-8105-3
  7. Embil JM, Papp K, Sibbald G, Tousignant J, Smiell JM, Wong B, Lau CY: Recombinant human platelet-derived growth factor-BB(becaplermin) for healing chronic lower extremity diabetic ulcers: an open-label clinical evaluation of efficacy. Wound Repair Regen 8: 162, 2000 https://doi.org/10.1046/j.1524-475x.2000.00162.x
  8. Kano M, Masuda Y, Tominaga T, Hori T, Kitaichi T, Yoshizumi M, Kitagawa T: Collagen synthesis and collagenase activity of cryopreserved heart valves. J Thorac Cardiovasc Surg 122: 706, 2001 https://doi.org/10.1067/mtc.2001.115421
  9. Wallace PM, MacMaster JF, Rouleau KA, Brown TJ, Loy JK, Donaldson KL, Wahl AF: Regulation of inflammatory response by oncostatin M. J Immunol 162: 5547, 1999
  10. Gomez-Lechon MJ: Oncostatin M: signal transduction and biological activity. Life Sci 65: 2019, 1999 https://doi.org/10.1016/S0024-3205(99)00296-9
  11. Heinrich PC, Behrmann I, Haan S, Hermanns HM, Müller-Newen G, Schaper F: Principles of interleukin (IL)-6-type cytokine signalling and its regulation. Biochem J 374: 1, 2003 https://doi.org/10.1042/BJ20030407
  12. Finelt N, Gazel A, Gorelick S, Blumenberg M: Transcriptional responses of human epidermal keratinocytes to Oncostatin-M. Cytokine 31: 305, 2005 https://doi.org/10.1016/j.cyto.2005.05.005
  13. Cohen M, Marchand-Adam S, Lecon-Malas V, Marchal- Somme J, Boutten A, Durand G, Crestani B, Dehoux M: HGF synthesis in human lung fibroblasts is regulated by oncostatin M. Am J Physiol Lung Cell Mol Physiol 290: 1097, 2006 https://doi.org/10.1152/ajplung.00166.2005
  14. Inh H, Tamaki K: Oncostatin M stimulates the growth of dermal fibroblasts via a mitogen-activated protein kinase-dependent pathway. J Immunol 165: 2149, 2000 https://doi.org/10.4049/jimmunol.165.4.2149
  15. Duncan MR, Hasan A, Berman B: Oncostatin M stimulates collagen and glycosaminoglycan production by cultured normal dermal fibroblasts: insensitivity of sclerodermal and keloidal fibroblasts. J Invest Dermatol 104: 128, 1995 https://doi.org/10.1111/1523-1747.ep12613623