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Stimulation by transforming growth factor-β of epidermal growth factor-dependent growth of aged human fibroblasts: Recovery of high affinity EGF receptors and growth stimulation by EGF

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Editor's statement TGF beta interaction with its receptor is known to affect EGF receptors. In this paper a functional biological association is established.

Summary

The stimulatory effects of transforming growth factor β (TGF-β) on epidermal growth factor (EGF)-dependent growth of adult and newborn human fibroblasts were investigated. EGF-stimulated growth in low serum of dermal fibroblasts from a 41 year-old adult (HSF-41) was less than half that of newborn foreskin fibroblasts (HFF). The EGF-stimulated growth of HFF after 55 population doublings (HFF-55) was similarly reduced. The decreased growth response to EGF of fibroblasts, agedin vivo andin vitro appeared to result principally from a decreased sensitivity to EGF due to a decreased number and affinity of high affinity EGF receptors (H-EGFR). Pre-incubation of HSF-41 and HFF-55 with 25 pM TGF-β enhanced the growth responses of these cells to EGF and increased the levels of high affinity EGF-binding by these cells Thus, the stimulation by TGF-β of EGF-dependent growth of human fibroblasts agedin vivo orin vitro is mediated by increased levels of high affinity EGF binding.

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References

  1. Sporn, M. B.; Roberts, A. B.; Wakefield, L. M., et al. Some recent advances in the chemistry and biology of transforming growth factor-beta. J. Cell. Biol. 105:1039–1045; 1987.

    Article  PubMed  CAS  Google Scholar 

  2. Massague, J. The TGF-beta family of growth and differentiation factors. Cell. 49:437–438; 1987.

    Article  PubMed  CAS  Google Scholar 

  3. Tucker, R. F.; Shipley, G. D.; Moses, H. L., et al. Growth inhibitor from BSC-1 cells closely related to platelet type-β transforming growth factor. Science 226:705–707; 1984.

    Article  PubMed  CAS  Google Scholar 

  4. Roberts, A. B.; Anzano, M. A.; Wakefield, L. M., et al. Type-β transforming growth factor: a bifunctional regulator of cellular growth. Proc. Natl. Acad. Sci. USA 82:119–123; 1985.

    Article  PubMed  CAS  Google Scholar 

  5. Assoian, R. K.. Biphasic effects of type-beta transforming growth factor on epidermal growth factor receptors in NRK fibroblasts: functional consequences for EGF-stimulated mitosis. J. Biol. Chem. 260:9613–9617; 1985.

    PubMed  CAS  Google Scholar 

  6. Ignotz, R. A.; Massague, J. Type β transforming growth factor controls the adipogenic differentiation of 3T3 fibroblasts. Proc. Natl. Acad. Sci. USA 82:2438–2442; 1986.

    Google Scholar 

  7. Masui, T.; Wakefield, L. M.; Lechner, J. F., et al. Type β transforming growth factor is the primary differentiation-inducing serum factor for normal human bronchial epithelial cells. Proc. Natl. Acad. Sci. USA 83:2438–2442; 1986.

    Article  PubMed  CAS  Google Scholar 

  8. Seyedin, S. M.; Segarini, P. R.; Rosen, D. M., et al. Cartilage-inducing factor-β is a unique protein structurally and functionally related to transforming growth factor-β. J. Biol. Chem. 262:1946–1949; 1987.

    PubMed  CAS  Google Scholar 

  9. Dodson, W. C.; Schomberg, D. W. The effect of transforming growth factor-β on follicle-stimulating hormone-induced differentiation of rat granulosa cells. Endocrinology 120:512–516; 1987.

    Article  PubMed  CAS  Google Scholar 

  10. Kimelman, D.; Kirschner, M. Synergistic induction of mesoderm by FGF and TGF-β and the identification of mRNA coding for FGF in the early Xenopus embryo. Cell. 51:869–877; 1987.

    Article  PubMed  CAS  Google Scholar 

  11. Boerner, P.; Resnick, R. J.; Racker, E. Stimulation of glycolysis and amino acid uptake in NRK-49F cells by transforming growth factor-β and epidermal growth factor. Proc. Natl. Acad. Sci. USA 82:1350–1353; 1985.

    Article  PubMed  CAS  Google Scholar 

  12. Inman, W. H.; Colowick, S. P. Stimulation of glucose uptake by transforming growth factor-β: evidence for the requirement of epidermal growth factor receptor activation. Proc. Natl. Acad. Sci. USA 82:1346–1349; 1985.

    Article  PubMed  CAS  Google Scholar 

  13. Roberts, A. B.; Sporn, M. B.; Assoian R. K., et al. Transforming growth factor type-β: rapid induction of fibrosis and angiogenesisin vivo and stimulation of collagen formationin vitro. Proc. Natl. Acad. Sci. USA 83:4167–4171; 1986.

    Article  PubMed  CAS  Google Scholar 

  14. Ignotz, R. A.; Massague, J. Transforming growth factor β-stimulates the expression of fibronectin and collagen and their incorporation into the extracellular matrix. J. Biol. Chem. 261:4337–4345; 1986.

    PubMed  CAS  Google Scholar 

  15. Centrella, M.; McCarthy, T. L.; Canalis, E. Transforming growth factor-β is a bifunctional regulator of replication and collagen synthesis in osteoblast-enriched cell cultures from fetal rat bone. J. Biol. Chem. 262:2869–2874; 1987.

    PubMed  CAS  Google Scholar 

  16. Fine, A.; Goldstein, R. H. The effect of transforming growth factor-β on cell proliferation and collagen formation by lung fibroblasts. J. Biol. Chem. 262:3897–3902; 1987.

    PubMed  CAS  Google Scholar 

  17. Varga, J.; Rosenbloom, J.; Jimenez, S. A. Transforming growth factor-β causes a, persistant increase in steady state amounts of type I and type III collagen and fibronectin mRNAs in normal human dermal fibroblasis. Biochem. J. 247:597–604; 1987.

    PubMed  CAS  Google Scholar 

  18. Noda, M.; Rodan, G. A. Type-β transforming growth factor inhibits proliferation, and expression of alkaline phosphatase in murine osteoblast-like cells. Biochem. Biophys. Res. Commun. 140:56–65; 1986.

    Article  PubMed  CAS  Google Scholar 

  19. Noda, M.; Rodan, G. A. Type-β transforming growth factor regulation of alkaline phosphatase expression and other phenotype-related mRNAs in osteoblastic rat osteosarcoma cells. J. Cell. Physiol. 133:426–437; 1987.

    Article  PubMed  CAS  Google Scholar 

  20. Sporn, M. B.; Roberts, A. B.; Wakefield, L. M., et al. Transforming growth factor-β: biological function and chemical structure. Science (Washington, DC) 233:532–534; 1986.

    Article  CAS  Google Scholar 

  21. Lee, K.; Tanaka, M.; Hatanka, M., et al. Reciprocal effects of EGF and TGF-β on the anchorage-dependent and anchorage-independent growth of A431 epidermoid carcinoma cells. Exp. Cell. Res. 173:156–162; 1987.

    Article  PubMed  CAS  Google Scholar 

  22. Willingham, M. C.; Maxfield, F. R.; Pastan, I. H. Alpha-2 macroglobulin, binding to the plasma membrane of cultured fibroblasts—diffuse binding followed by clustering in coated regions. J. Cell. Biol. 82:614–625; 1979.

    Article  PubMed  CAS  Google Scholar 

  23. Kawamoto, T.; Sato, J. D.; Le, A., et al. Growth-stimulation of A431 cells by epidermal growth factor: identification of high-affinity receptors for EGF by an anti-receptor monoclonal antibody. Proc. natl. Acad. Sci. USA 80:1337–1341; 1983.

    Article  PubMed  CAS  Google Scholar 

  24. Comens, P. G.; Simmer, R. L.; Baker, J. B. Direct linkage of125I-EGF to cell surface receptors—a useful artifact of chloramine T treatment. J. Biol. Chem. 257;42–45; 1982.

    PubMed  CAS  Google Scholar 

  25. Schneider, E. L.; Matsui, Y. Relationship betweenin vitro cellular aging andin vivo human age. Proc. Natl. Acad. Sci. USA 73:3587–3588; 1976.

    Article  Google Scholar 

  26. Stanulis-Praeger, B. M. Cellular senescence revisited. Mech. Aging Dev. 38:1–48; 1987.

    Article  PubMed  CAS  Google Scholar 

  27. Plisko, A.; Gilchrest, B. M. Growth factor responsiveness of cultured human fibroblasts declines with age. J. Gerontol. 38:513–518; 1983.

    PubMed  CAS  Google Scholar 

  28. Phillips, P. D.; Kaji, K.; Cristofalo, V. J. Progressive loss of the proliferative response of senescing WI-38 cells to PDGF, EGF, insulin, transferrin and dexamethasone. J. Gerontol. 39:11–17; 1984.

    PubMed  CAS  Google Scholar 

  29. Carlin, C. R.; Phillips, P. D.; Knowles, B. B., et al. Diminishedin vitro tyrosine kinase-activity of the EGF receptor of senescent human fibroblasts. Nature 306:617–620; 1983.

    Article  PubMed  CAS  Google Scholar 

  30. Assoian, R. K.; Frolik, C. A.; Roberts, A. B., et al. Transforming growth factor-β controls receptor levels for EGF in NRK fibroblasts. Cell 36:35–41; 1984.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Dept. of Biochemistry, Okayama University Dental School, 700, Okayama, Japan

    Tomoyuki Kawamoto, Kojiro Takahashi & Shigehiko Taniguchi

  2. Biochemical Research Center, Okayama University Dental School, 700, Okayama, Japan

    Mieko Nishi

  3. Shiseido Basic Research Laboratories, 233, Yokohama, Japan

    Toshio Nishiyama

  4. W. Alton Jones Cell Science Center, Inc., 12946, Lake Placid, NY

    J. Denry Sato

Authors
  1. Tomoyuki Kawamoto
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  2. Mieko Nishi
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  3. Kojiro Takahashi
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  4. Toshio Nishiyama
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  5. J. Denry Sato
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  6. Shigehiko Taniguchi
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Additional information

This research was supported in part by a grant-in-aid for scientific research (61480388) and a special project research grant to Okayama University from the Japanese Ministry of Education, Science and Culture.

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Kawamoto, T., Nishi, M., Takahashi, K. et al. Stimulation by transforming growth factor-β of epidermal growth factor-dependent growth of aged human fibroblasts: Recovery of high affinity EGF receptors and growth stimulation by EGF. In Vitro Cell Dev Biol 25, 965–970 (1989). https://doi.org/10.1007/BF02624011

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