Original Article

Journal of Investigative Dermatology (1995) 104, 241–245; doi:10.1111/1523-1747.ep12612788

Glucocorticoid Regulation of Elastin Synthesis in Human Fibroblasts: Down-Regulation in Fibroblasts from Normal Dermis But Not From Keloids

Shirley B Russell1, Joel S Trupin2, Rita Z Kennedy3, James D Russell2 and Jeffrey M Davidson3,4

  1. 1Department of Microbiology, Meharry Medical College, Nashville, Tennessee, U.S.A.
  2. 2Division of Biomedical Sciences, Meharry Medical College, Nashville, Tennessee, U.S.A.
  3. 3Department of Pathology, Vanderbilt University School of Medicine, Nashville, Tennessee, U.S.A.
  4. 4Research Service, Department of Veterans Affairs Medical Center, Nashville, Tennessee, U.S.A.

Received 30 September 1993; Revised 3 August 1994; Accepted 6 September 1994.

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Abstract

Keloids arise as benign connective tissue masses at sites of injury in genetically predisposed individuals, In addition to excessive collagen accumulation, there is biochemical and histologic evidence of elastic tissue. Previous studies showed that glucocorticoid regulation of collagen synthesis differs in fibroblasts from normal adult dermis and keloids, To define further the abnormal regulation of matrix synthesis in keloid fibroblasts, we examined glucocorticoid regulation of elastin synthesis. The basal level of elastin synthesis was significantly higher in keloid than in normal cells, and hydrocortisone reduced synthesis of elastin and elastin mRNA in normal but not in keloid fibroblasts. We had shown previously that fibroblasts from fetal dermis resembled keloid fibroblasts in glucocorticoid regulation of growth and collagen synthesis. In this study, glucocorticoids failed to down-regulate elastin synthesis in fetal cells that had not differentiated to produce normal levels of elastin, whereas fetal cells with normal elastin production exhibited glucocorticoid down-regulation. Abnormal regulation in keloid cells was independent of cell density and was confined to fibroblasts cultured from the keloid nodule. These findings reinforce the conclusion that a matrix-regulatory pathway is deranged in these focal lesions. Coordinate down-regulation of collagen and elastin by hydrocortisone in normal adult denial fibroblasts and the failure of hydrocortisone to down-regulate synthesis of either protein in keloid cells support the existence of common elements in the regulatory pathways of these two matrix proteins.

Keywords:

extracellular matrix, fetal fibroblasts, wound healing

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References

  1. Robert, L, Hornebeck, W (eds.): Elastin and Elastases I and II: CRC Press, Boca Raton, FL, 1989
  2. Holbrook, KA: Developmental landmarks in the ontogeny of human embryonic and fetal skin: implications for prenatal diagnosis of inherited skin disease. In: Abatangelo G, Davidson JM (eds.). Cutaneous Development, Aging and Repair Liviana Press, Padova, Italy, pp 245–262, 1989
  3. Davidson, JM, Giro, MG: Control of elastin synthesis: molecular and cellular aspects. In: Mecham RP (ed.). Regulation of Matrix Accumulation Academic Press, Orlando, FL, pp 177–216, 1986
  4. Davidson, JM: Regulation of elastin gene expression. In: Robert L, Hornebeck W (eds.). Elastin and Elastases I: CRC Press, Boca Raton. FL, pp 83–90, 1989
  5. Davidson, JM, Giro, MG, Quaglino, D: Repair of elastic tissue. In: Cohen IK, Diegelmann RF, Lindblad WJ (eds.). Wound Healing: Biochemical & Clinical Aspects WB Saunders, Philadelphia, pp 223–236, 1992
  6. Sephel, GC, Buckley, A, Davidson, JM: Developmental initiation of elastin gene expression by human fetal skin fibroblasts. J Invest Dermatol 88: 732–735, 1987 | Article | PubMed | ISI | ChemPort |
  7. Sephel, GC, Davidson, JM: Elastin production in human skin fibroblast cultures and its decline with age. J Invest Dermatol 86: 279–285, 1986 | Article | PubMed | ISI | ChemPort |
  8. Fazio, MJ, Olsen, DR, Kuivaniemi, H, Chu, M-L, Davidson, JM, Rosenbloom, J, Uitto, J: Isolation and characterization of human elastin cDNA's, and age associated variation in elastin gene expression in cultured skin fibroblasts. Lab Invest 58: 270–277, 1988
  9. Davidson, JM, Zoia, O, Liu, J-M: Modulation of transforming growth factorbeta 1 stimulated elastin and collagen production and proliferation in porcine vascular smooth muscle cells and skin fibroblasts by basic fibroblast growth factor, transforming growth factor-alpha, and insulin-like growth factor-1. J Cell Physiol 155: 149–156, 1993
  10. Liu, J, Davidson, JM: The elastogenic effect of recombinant transforming growth factor beta on porcine aortic smooth muscle cells. Biochem Biophys Res Commun 154: 895–901, 1988
  11. Foster, J, Rich, CB, Florini, JR: Insulin-like growth factor I, somatomedin C, induces the synthesis of tropoelastin in aortic tissue. Collagen Rel Res 7: 161–169, 1987
  12. Kähäri, V-M, Chen, YQ, Bashir, MM, Rosenbloom, J, Uitto, J: Tumor necrosis factor-alpha down-regulates human elastin gene expression. J Biol Chem 267: 26134–26141, 1992 | PubMed | ISI | ChemPort |
  13. Berk, JL, Franzblau, C, Goldstein, RH: Recombinant interleukin-1beta inhibits elastin formation by a neonatal rat lung fibroblast subtype. J Biol Chem 266: 3192–3197, 1991 | PubMed | ChemPort |
  14. Mauviel, A, Chen, YQ, Kähäri, V-M, Ledo, I, Wu, M, Rudnicka, L, Uitto, J: Human recombinant interleukin-lbeta up-regulates elastin gene expression in dermal fibroblasts. J Biol Chem 268: 6520–6524, 1993 | PubMed | ISI | ChemPort |
  15. Parks, WC, Pierce, RA, Lee, KA, Mecham, RP: Elastin. In: Kleinman HK (ed.). Advances in Molecular and Cell Biology 6: JAI Press, Greenwich, Connecticut, pp 133–182, 1993
  16. Murray, JC, Pollack, SV, Pinnell, SR: Keloids: a review. J Am Acad Dermatol 4: 461–470, 1981 | PubMed | ISI | ChemPort |
  17. Datubo-Brown, DD: Keloids: a review of the literature. Br J Plast Surg 43: 70–77, 1990 | PubMed | ChemPort |
  18. Kischer, CW, Hendrix, MJC: Fibronectin (FN) in hypertrophic scars and keloids. Cell Tissue Res 231: 29–37, 1983 | PubMed | ISI | ChemPort |
  19. Bazin, S, Nicoletis, C, Delaunay, A: Intercellular matrix of hypertrophic scars and keloids. In: Kulonen E, Pikkarainen J (eds.). Biology of Fibroblast Academic Press. New York, pp 571–571, 1973
  20. Diegelmann, RF, Cohen, IK, McCoy, BJ: Growth kinetics and collagen synthesis of normal skin, normal scar and keloid fibroblasts in vitro. J Cell Physiol 98: 341–346, 1979 | Article | PubMed | ISI | ChemPort |
  21. Abergel, RP, Pizzurro, D, Meeker, CA, Lask Matsuoka, LY, Minor, RR, Chu, M-I, Uitto, J: Biochemical composition of the connective tissue in keloids and analysis of collagen metabolism in keloid fibroblast cultures. J Invest Dermatol 84: 381–390, 1985
  22. Babu, M, Diegelmann, R, Oliver, N: Fibronectin is overproduced by keloid fibroblasts during abnormal wound healing. Mol Cell Biol 9: 1642–1650, 1989 | PubMed | ISI | ChemPort |
  23. Russell, JD, Russell, SB, Trupin, KM: Differential effects of hydrocortisone on both growth and collagen metabolism of human fibroblasts from normal and keloid tissue. J Cell Physiol 97: 221–230, 1978 | Article | PubMed | ISI | ChemPort |
  24. Trupin, JS, Russell, SB, Russell, JD: Variation in prolyl hydroxylase activity of keloid-derived and normal human fibroblasts in response to hydrocortisone and ascorbic acid. Collagen Rel Res 3: 13–23, 1983
  25. Russell, SB, Trupin, JS, Myers, JC, Broquist, AH, Smith, JC, Myles, ME, Russell, JD: Differential glucocorticoid regulation of collagen mRNAs in human dermal fibroblasts. J Biol Chem 264: 13730–13735, 1989 | PubMed | ISI | ChemPort |
  26. Ala-Kokko, L, Rintala, A, Savolainen, E-R: Collagen gene expression in keloids: analysis of collagen metabolism and type I, III, IV, and V procollagen mRNAs in keloid tissue and keloid fibroblast cultures. J Invest Dermatol 89: 238–244, 1987 | Article | PubMed | ChemPort |
  27. Russell, SB, Trupin, KM, Rodriguez-Eaton, S, Russell, JD, Trupin, JS: Reduced growth-factor requirement of keloid-derived fibroblasts may account for tumor growth. Proc Natl Acad Sci USA 85: 587–591, 1988 | PubMed | ChemPort |
  28. Bhangoo, KS, Quinlivan, JK, Connelly, JR: Elastin fibers in scar tissue. Plast Reconstr Surg 57: 308–313, 1976
  29. Keely, FW, Johnson, DJ: Age differences in the effect of hydrocortisone on the synthesis of insoluble elastin in aortic tissue of growing chicks. Connect Tissue Res 16: 259–268, 1987
  30. Giro, MG, Oikarinen, AI, Oikarinen, H, Sephel, G, Uitto, J, Davidson, JM: Demonstration of elastin gene expression in human skin fibroblast cultures and reduced tropoelastin production by cells from a patient with atrophoderma. J Clin Invest 75: 672–678, 1985 | PubMed | ISI | ChemPort |
  31. Chu, M-L, Myers, JC, Bernard, MP, Ding, J-F, Ramirez, F: Cloning and characterization of five overlapping cDNAs specific for the human proalpha 1(I) collagen chain. Nucleic Acids Res 10: 5925–5934, 1982 | PubMed | ISI | ChemPort |
  32. Burton, K: Determination of DNA concentration with diphenylamine. Methods Enzymol 12: 163–166, 1968
  33. Franzblau, C, Mogayzel, PJ Jr, Paris, B, Barone, LM, Bergethon, PR: Regulation of elastin biosynthesis by vitamins and hormones. In: Robert L, Hornebeck W (eds.). Elastin and Elastases CRC Press, Boca Raton, FL, pp 91–108, 1989
  34. Eichner, R, Rosenbloom, J: Collagen and elastin synthesis in the developing chick aorta. Arch Biochem Biophys 198: 414–423, 1979
  35. Gabbiani, G, Rungger-Brändle, E: The fibroblast. In: Glynn LE (ed.). Tissue Repair and Regeneration Elsevier/North Holland Biomedical Press, Amsterdam, pp 1–50, 1981
  36. James, WD, Besanceney, CD, Odom, RB: The ultrastructure of a keloid. J Am Acad Dermatol 3: 50–57, 1980
  37. Leitman, DC, Benson, SC, Johnson, LK: Glucocorticoids stimulate collagen and noncollagen protein synthesis in cultured vascular smooth muscle cells. J Cell Biol 98: 541–549, 1984
  38. Broadley, C, Gonzalez, DA, Nair, R, Koriwchak, MJ, Ossoff, RH, Davidson, JM: A tissue culture model for the study of canine vocal fold fibroblasts. Laryngoscope 104: 1–5, 1994

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