Archives of Dermatological Research

, Volume 277, Issue 5, pp 373–376 | Cite as

Collagen synthesis in scleroderma: Selection of fibroblast populations during subcultures

  • T. Krieg
  • J. S. Perlish
  • R. Fleischmajer
  • O. Braun-Falco
Original Contributions


In progressive systemic scleroderma, excessive deposition of collagen leads to fibrosis of several tissues including the skin. It has been found that different populations of fibroblasts are present in scleroderma skin; these can be obtained by establishing cell cultures from different layers of the involved skin. Excessive overproduction of collagen was noted in primary cultures of cells obtained from deeper layers of the skin of patients in an early stage of the disease, whereas control fibroblasts did not manifest significant variations dependent on the layers of skin used to initiate the cultures. The synthesis of type-I and-III collagen was found to be altered concomitantly. The production of collagen and collagenous proteins was then followed during subcultivations of overproducing fibroblasts. In many cell strains, increased synthesis of collagen and/or noncollagenous proteins had already been lost after the first subcultivation, whereas overproduction was stable in others. However, after five passages, most of the cultures showed normal collagen synthesis, which probably indicates a loss of phenotype due to successive subcultures or overgrowth by another population of fibroblasts.

Key words

Collagen Fibroblast populations Scleroderma 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Bonner WM, Lasky RA (1974) A film-detection method for tritium-labelled proteins and nucleic acids in polyacrylamide gels. Eur J Biochem 46:83–88Google Scholar
  2. 2.
    Buckingham RB, Prince RK, Rodnan GP, Taylor F (1978) Increased collagen accumulation in dermal fibroblast cultures from patients with progressive systemic sclerosis (scleroderma). J Lab Clin Med 92:5–21Google Scholar
  3. 3.
    Buckingham RB, Prince RK, Rodnan GP, Barnes EC (1980) Collagen accumulation by dermal fibroblast cultures of patients with linear localized scleroderma. J Rheumatol 7:130–142Google Scholar
  4. 4.
    Fleischmajer R (1971) The pathophysiology in scleroderma. Int J Dermatol 16:310–318Google Scholar
  5. 5.
    Fleischmajer R, Nedwich A (1972) Generalized morphea. I. Histology of the dermis and subcutaneous tissue. Arch Dermatol 106:509–514Google Scholar
  6. 6.
    Fleischmajer R, Perlish JS, Krieg T, Timpl R (1981) Variability in collagen and fibronectin synthesis by scleroderma fibroblasts in primary culture. J Invest Dermatol 76:400–403Google Scholar
  7. 7.
    Fleischmajer R, Perlish JS, Duncan M (1984) Scleroderma: a model for fibrosis. Arch Dermatol (in press)Google Scholar
  8. 8.
    Krieg T, Muller PK, Goerz G (1977) Fibroblasts from a patient with scleroderma reveal abnormal metabolism. Arch Dermatol Res 259:105–107Google Scholar
  9. 9.
    Krieg T; Aumailley M, Dessau M, Wiestner M, Muller P (1980) Synthesis of collagen by human fibroblast and their SV-40 tranformants. Exp Cell Res 125:23–31Google Scholar
  10. 10.
    Krieg T, Braun-Falco O, Perlish JS, Fleischmajer R (1983) Collagen synthesis in generalized morphea. Arch Dermatol Res 275:393–396Google Scholar
  11. 11.
    Laemmli HK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680–685Google Scholar
  12. 12.
    Layman DL, McGoodwin EB, Martin GR (1971) The nature of the collagen synthesized by cultured human fibroblasts. Proc Natl Acad Sci USA 68:454–458Google Scholar
  13. 13.
    LeRoy C (1974) Increased collagen synthesis by scleroderma fibroblasts in vitro. J Clin Invest 54:880–889Google Scholar
  14. 14.
    Lowry OH, Rosebrough NJ, Farr AC, Randall RJ (1951) Protein measurement with the Folin phenol reagent J Biol Chem 193:265–275Google Scholar
  15. 15.
    Perlish JS, Bashey RJ, Stephens RE, Fleischmajer R (1976) Connective-tissue synthesis by cultured scleroderma fibroblsts. 1. In vitro collagen synthesis by normal and scleroderma dermal fibroblasts. Arthritis Rheum 195:891–901Google Scholar
  16. 16.
    Uitto J, Bauer E, Eisen A (1979) Scleroderma: increased biosynthesis of triple-helical type-I and type-III procollagens associated with unaltered expression of collagenase by skin fibroblasts in culture. J Clin Invest 64:921–930Google Scholar
  17. 17.
    Wiestner M, Krieg T, Hörlein D, Glanville R, Fietzek P, Muller P (1979) Inhibiting effect of procollagen peptides on collagen biosynthesis in fibroblasts cultures. J Biol Chem 254:7016–7023Google Scholar
  18. 18.
    Winkelmann RK (1976) Pathogenesis and staging of scleroderma. Acta Derm Venereol (Stockh) 56:83–92Google Scholar

Copyright information

© Springer-Verlag 1985

Authors and Affiliations

  • T. Krieg
    • 1
    • 2
  • J. S. Perlish
    • 3
  • R. Fleischmajer
    • 3
  • O. Braun-Falco
    • 1
  1. 1.Dermatologische Klinik der Ludwig-Maximilians-Universität MünchenMünchenGermany
  2. 2.Abteilung BindegewebsforschungMax-Planck-Institut für BiochemieMartinsriedGermany
  3. 3.Department of DermatologyMount Sinai Medical SchoolNew YorkUSA

Personalised recommendations