Skip to main content
SpringerLink
Log in

A decrease in hyaluronic acid synthesis by aging human fibroblasts leading to heparan sulfate enrichment and growth reduction

  • Original Articles
  • Published:
Aging Clinical and Experimental Research Aims and scope Submit manuscript

Abstract

Cultured normal human fibroblasts during in vitro aging exhibited increased proportions of heparan sulfate (HS; a glycosaminoglycan (GAG) species) in the cell-associated GAG pool, coincident with decreased cell growth activity. An analysis of GAG metabolism demonstrated that human fibroblasts during aging became relatively rich in HS due to an alteration in the profile of GAG synthesis. HS became relatively enriched and hyaluronic acid (HA) relatively depleted through a decrease in HA synthase activity. An experimental enrichment of human fibroblast cultures with exogenous HS brought about an arrest of the cells in the G0/G1 phase and a decrease in the rate of S phase entry, coincident with aged cell growth behaviour. These results suggest that the change in HA synthesis is responsible, at least to some extent, for the growth reduction during aging of normal human fibroblasts.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Hayflick L.: The limited in vitro lifetime of human diploid cell strains. Exp. Cell. Res. 37: 614–636, 1965.

    Article  PubMed  CAS  Google Scholar 

  2. Smith J.R., Lincoln II D.W.: Aging of cells in culture. Int. Rev. Cytol. 89: 151–177, 1984.

    Article  PubMed  CAS  Google Scholar 

  3. Sluke G., Schachtschabel D.O., Wever J.: Age-related changes in the distribution pattern of glycosaminoglycans synthesized by cultured human diploid fibroblasts (WI-38). Mech. Ageing Develop. 16: 19–27, 1981.

    Article  CAS  Google Scholar 

  4. Matuoka K., Mitsui Y.: Changes in cell-surface glycosaminoglycans in human diploid fibroblasts during in vitro aging. Mech. Ageing Develop. 15: 153–163, 1981.

    Article  CAS  Google Scholar 

  5. Matuoka K., Mitsui Y.: Involvement of cell surface heparan sulfate in the density-dependent inhibition of cell proliferation. Cell Struct. Funct. 6: 23–33, 1981.

    Article  CAS  Google Scholar 

  6. Fritze L.M.S., Reilly C.F., Rosenberg R.D.: An antiproliferative heparan sulfate species produced by postconfluent smooth muscle cells. J. Cell. Biol. 100: 1041–1049, 1985.

    Article  PubMed  CAS  Google Scholar 

  7. Ishihara M., Fedarko N.S., Conrad H.E.: Involvement of phosphatidylinositol and insulin in the coordinate regulation of proteoheparan sulfate metabolism and hepatocyte growth. J. Biol. Chem. 262: 4708–4716, 1987.

    PubMed  CAS  Google Scholar 

  8. Gallagher J.T., Lyon M., Steward W.P.: Structure and function of heparan sulfate proteoglycans. Biochem. J. 236: 313–325, 1986.

    PubMed  CAS  Google Scholar 

  9. Schachtschabel D.O., Sluke G.: Increase of cellular hyaluronic acid synthesis following continuous exposure of cultured human fibroblasts (WI-38) to hydrocortisone. Z. Gerontol. 19: 173–178, 1986.

    PubMed  CAS  Google Scholar 

  10. Matuoka K., Namba M., Mitsui Y.: Hyaluronate synthetase inhibition by normal and transformed human fibroblasts during growth reduction. J. Cell. Biol. 104: 1105–1115, 1987.

    Article  PubMed  CAS  Google Scholar 

  11. Ohashi M., Aizawa S., Ooka H.: A new human diploid cell strain, TIG-1, for the research on cellular aging. Exp. Gerontol. 14: 121–133, 1980.

    Article  Google Scholar 

  12. Namba M., Nishitani K., Kimoto T.: Characteristics of WI-38 cells (WI-38 CT-1) transformed by treatment with Co-60 gamma rays. Gann (Jpn. J. Cancer Res.) 71: 300–307, 1980.

    CAS  Google Scholar 

  13. Matuoka K., Mitsui Y., Murota S.: Heparan sulfate enhances growth of transformed human fibroblasts. Cell Struct. Funct. 9: 357–367, 1984.

    Article  PubMed  CAS  Google Scholar 

  14. Smith J.A., Martin L.: Do cells cycle? Proc. Natl. Acad. Sci. USA 70: 1263–1267, 1973.

    Article  PubMed  CAS  Google Scholar 

  15. Matuoka K., Mitsui Y., Murota S.: Growth-coupled changes in glucosaminoglycans (heparan sulfate and hyaluronic acid) in normal and transformed human fibroblasts. Cell. Biol. Int. Rep. 9: 577–586, 1985.

    Article  PubMed  CAS  Google Scholar 

  16. Fried J., Perez A.G., Glarkson B.D.: Flow cytometric analysis of cell cycle distribution using propidium iodide. Properties of the method and mathematical analysis of the data. J. Cell. Biol. 71: 172–181, 1976.

    Article  PubMed  CAS  Google Scholar 

  17. Macieira-Coelho A.: Changes in membrane properties associated with cellular aging. Int. Rev. Cytol. 83: 183–220, 1983.

    Article  PubMed  CAS  Google Scholar 

  18. Tomida M., Koyama H., Ono T.: Induction of hyaluronic acid synthetase activity in rat fibroblasts by medium change of confluent cultures. J. Cell. Physiol. 86: 121–130, 1975.

    Article  PubMed  CAS  Google Scholar 

  19. Moscatelli D., Rubin H.: Hormonal control of hyaluronic acid production in fibroblasts and its relation to nucleic acid and protein synthesis. J. Cell Physiol. 91: 79–88, 1977.

    Article  PubMed  CAS  Google Scholar 

  20. Matuoka K., Mitsui Y., Murota S., Namba M.: Actions of exogenous heparan sulfate and hyaluronic acid on growth and thymidine incorporation of normal and transformed human fibroblasts. Cell. Biol. Int. Rep. 9: 815–824, 1985.

    Article  PubMed  CAS  Google Scholar 

  21. Schachtschabel D.O., Wever J., Sluke G., Wever G.: Influence of exogenous glycosaminoglycans on growth and glycosaminoglycan synthesis of cultured human diploid fibroblasts (WI-38). Z. Gerontol. 12: 19–26, 1979.

    PubMed  CAS  Google Scholar 

  22. Wever J., Schachtschabel D.O., Sluke G., Wever G.: Effect of short- or long-term treatment with exogenous glycosaminoglycans on growth and glycosaminoglycan synthesis of human fibroblasts (WI-38) in culture. Mech. Ageing Develop. 14: 89–99, 1980.

    Article  CAS  Google Scholar 

  23. Griffiths T.D.: S-phase transit times as a function of age in human diploid fibroblasts. Mech.Ageing Develop. 24: 273–282, 1984.

    Article  CAS  Google Scholar 

  24. Cunningham D.D., Remo R.A.: Specific increase in ribonucleic acid synthesis in 3T3 mouse cells. J. Biol. Chem. 248: 6282–6288, 1973.

    PubMed  CAS  Google Scholar 

  25. Grove G.L., Cristofalo V.J.: Characterization of the cell cycle of cultured human diploid cells: Effects of aging and hydrocortisone. J. Cell. Physiol. 90: 415–422, 1977.

    Article  PubMed  CAS  Google Scholar 

  26. Rittling S.R., Brooks K.M., Cristofalo V.J., Baserga R.: Expression of cell cycle-dependent genes in young and senescent WI-38 fibroblasts. Proc. Natl. Acad. Sci. USA 83: 3316–3320, 1986.

    Article  PubMed  CAS  Google Scholar 

  27. Gorman S.D., Cristofalo V.J.: Analysis of the G1 arrest position of senescent WI38 cells by quinacrine dihydrochloride nuclear fluorescence. Evidence for a late G1arrest. Exp. Cell. Res. 167: 87–94, 1986.

    Article  PubMed  CAS  Google Scholar 

  28. Macieira-Coelho A.: Action of cortisone on human fibroblasts in vitro. Experimentia 22: 390–391, 1966.

    CAS  Google Scholar 

  29. Mian N.: Characterization of a high-Mr plasma-membrane-bound protein and assessment of its role as a constituent of hyaluronate synthase complex. Biochem. J. 237: 343–357, 1986.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. School of Pathology, University of New South Wales, P.O. Box 1, Kensington, NSW, 2033, Australia

    Koozi Matuoka & G. J. Smith

  2. Division of Cell Biology, Yakult Central Institute for Microbiological Research, Japan

    N. Hasegawa

  3. Department of Pathology, Kawasaki Medical School, Japan

    M. Namba

  4. Cell Science and Technology Division, Fermentation Research Institute, Japan

    Y. Mitsui

Authors
  1. Koozi Matuoka
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. N. Hasegawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. Namba
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. G. J. Smith
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Y. Mitsui
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Matuoka, K., Hasegawa, N., Namba, M. et al. A decrease in hyaluronic acid synthesis by aging human fibroblasts leading to heparan sulfate enrichment and growth reduction. Aging Clin Exp Res 1, 47–54 (1989). https://doi.org/10.1007/BF03323875

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03323875

Keywords

Search

Navigation