Suppression of experimental glomerulonephritis by antiserum against transforming growth factor β1

Abstract

GLOMERULONEPHRITIS is an inflammation of the kidney characterized by the accumulation of extracellular matrix within the damaged glomeruli1–4, impaired filtration and proteinuria. In its progressive form, the disease destroys kidney function leading to uraemia and death, unless dialysis therapy or kidney transplantation is available. The pathogenesis of glomerulonephritis is incompletely understood, but the eliciting factor is thought often to be an immunological injury to mesangial and/or other resident cells in the glomeruli5,6. We have used an animal model of acute mesangial proliferative glomerulonephritis7,8 to show that this disease is associated with increased production and activity of transforming growth factor β1 (TGF-βl)9, an inducer of extracellular matrix production10–17. Here we report that administration of anti-TGF-βl at the time of induction of the glomerular disease suppresses the increased production of extracellular matrix and dramatically attenuates histological manifestations of the disease. These results provide direct evidence for a causal role of TGF-βl in the pathogenesis of the experimental disease and suggest a new approach to the therapy of glomerulonephritis.

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References

  1. 1

    Bruijn, J. A., Hogendoorn, P. C., Hoedemaeker, P. J. & Fleuren, G. J. J. Lab. clin. Med. 111, 140–149 (1988).

    CAS  PubMed  Google Scholar 

  2. 2

    Klahr, S., Schreiner, G. & Ichikawa, I. New Engl. J. Med. 318, 1657–1666 (1988).

    CAS  Article  Google Scholar 

  3. 3

    Striker, L. M. M., Killen, P. D., Chi, E. & Striker, G. E. Lab. Invest. 51, 181–192 (1984).

    PubMed  Google Scholar 

  4. 4

    Diamond, J. R. & Karnovsky, M. J. Kidney Int. 33, 917–924 (1988).

    CAS  Article  Google Scholar 

  5. 5

    Couser, W. G. Kidney Int. 28, 569–583 (1985).

    CAS  Article  Google Scholar 

  6. 6

    Andres, G., Brentjens, J. R., Caldwell, P. R., Camussi, G. & Matsuo, S. Lab. Invest. 55, 510–520 (1986).

    CAS  PubMed  Google Scholar 

  7. 7

    Bagchus, W. M., Hoedemaeker, P. J., Rozing, J. & Bakker, W. W. Lab. Invest. 55, 680–687 (1986).

    CAS  PubMed  Google Scholar 

  8. 8

    Yamamoto, T. & Wilson, C. B. Kidney Int. 32, 514–525 (1987).

    CAS  Article  Google Scholar 

  9. 9

    Okuda, S., Languino, L. R., Ruoslahti, E. & Border, W. A. J. clin. Invest. (in the press).

  10. 10

    Ignotz, R. A. & Massague, J. J. biol. Chem. 261, 4337–4345 (1986).

    CAS  PubMed  Google Scholar 

  11. 11

    Roberts, A. B. et al. Proc. natn. Acad. Sci. U.S.A. 83, 4167–4171 (1986).

    ADS  CAS  Article  Google Scholar 

  12. 12

    Massague, J. Cell 49, 437–438 (1987).

    CAS  Article  Google Scholar 

  13. 13

    Ignotz, R. A. & Massague, J. Cell 51, 189–197 (1987).

    CAS  Article  Google Scholar 

  14. 14

    Sporn, M. B., Roberts, A. B., Wakefield, L. M. & de Crombrugghe, B. J. Cell Biol. 105, 1039–1044 (1987).

    CAS  Article  Google Scholar 

  15. 15

    Keski-Oja, J., Leof, E. B., Lyons, R. M., Coffey, R. J. & Moses, H. L. J. Cell Biochem. 33, 95–107 (1987).

    CAS  Article  Google Scholar 

  16. 16

    Roberts, C. et al. J. biol. Chem. 263, 4586–4592 (1988).

    CAS  PubMed  Google Scholar 

  17. 17

    Border, W. A., Okuda, S., Languino, L. R. & Ruoslahti, E. Kidney Int. 37, 689–695 (1990).

    CAS  Article  Google Scholar 

  18. 18

    Flanders, K. C., Roberts, A. B., Ling, N., Fleurdelys, B. E. & Sporn, M. B. Biochemistry 27, 739–746 (1988).

    CAS  Article  Google Scholar 

  19. 19

    Flanders, K. C. et al. J. Cell Biol. 108, 653–660 (1989).

    CAS  Article  Google Scholar 

  20. 20

    Bassols, A. & Massague, J. J. biol. Chem. 263, 3039–3045 (1988).

    CAS  PubMed  Google Scholar 

  21. 21

    Morales, T. I. & Roberts, A. B. J. biol. Chem. 263, 12828–12831 (1988).

    CAS  PubMed  Google Scholar 

  22. 22

    Czaja, M. J. et al. J. Cell Biol. 108, 2477–2482 (1989).

    CAS  Article  Google Scholar 

  23. 23

    MacKay, K. et al. J. clin. Invest. 82, 1160–1167 (1989).

    Article  Google Scholar 

  24. 24

    Derynck, R. et al. Nature 316, 701–705 (1985).

    ADS  CAS  Article  Google Scholar 

  25. 25

    Nakamura, T., Okuda, S., Miller, D., Ruoslahti, E. & Border, W. Kidney Int. 37, 221 (1990) (abstr.).

    Google Scholar 

  26. 26

    Laiho, M., Saksela, O., Andreasen, P. A. & Keski-Oja, J. J. Cell Biol. 103, 2403–2410 (1986).

    CAS  Article  Google Scholar 

  27. 27

    Edwards, D. R. et al. EMB0 J. 6, 1899–1904 (1987).

    CAS  Article  Google Scholar 

  28. 28

    Border, W. A. Kidney Int. 34, 419–434 (1988).

    CAS  Article  Google Scholar 

  29. 29

    Cheifetz, S. et al. Cell 48, 409–415 (1987).

    CAS  Article  Google Scholar 

  30. 30

    Benoit, R. et al. Proc. natn. Acad. Sci. U.S.A. 79, 917 (1982).

    ADS  CAS  Article  Google Scholar 

  31. 31

    Raij, L., Azar, S. & Keane, W. Kidney Int. 26, 137–143 (1984).

    CAS  Article  Google Scholar 

  32. 32

    Mauer, S. J. et al. J. clin. Invest. 74, 1143–1155 (1984).

    CAS  Article  Google Scholar 

  33. 33

    Chirgwin, J. M., Przybyla, A. E., MacDonald, R. J. & Rutter, W. J. Biochemistry 18, 5294–5299 (1979).

    CAS  Article  Google Scholar 

  34. 34

    Kondaiah, P. E. et al. J. biol. Chem. 263, 18313–18317 (1988).

    CAS  PubMed  Google Scholar 

  35. 35

    Fort, Ph. et al. Nucleic Acids Res. 13, 1431–1443 (1985).

    CAS  Article  Google Scholar 

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Border, W., Okuda, S., Languino, L. et al. Suppression of experimental glomerulonephritis by antiserum against transforming growth factor β1. Nature 346, 371–374 (1990). https://doi.org/10.1038/346371a0

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