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Natural inhibitor of transforming growth factor-β protects against scarring in experimental kidney disease

Nature volume 360, pages 361–364 (1992)Cite this article

Abstract

THE central pathological feature of human kidney disease that leads to kidney failure is the accumulation of extracellular matrix in glomeruli. Overexpression of transforming growth factor-β (TGF-β) underlies the accumulation of pathological matrix in experimental glomerulonephritis1. Administration of an antibody raised against TGF-β to glomerulonephritic rats suppresses glomerular matrix production and prevents matrix accumulation in the injured glomeruli2. One of the matrix components induced by TGF-β, the proteoglycan decorin, can bind TGF-β and neutralize its biological activity3, so decorin may be a natural regulator of TGF-β (refs 3,4). We tested whether decorin could antagonize the action of TGF-β in vivo using the experimental glomerulonephritis model1. We report here that administration of decorin inhibits the increased production of extracellular matrix and attenuates manifestations of disease, confirming our hypothesis. On the basis of our results, decorin may eventually prove to be clinically useful in diseases associated with overproduction of TGF-β.

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Authors and Affiliations

  1. Division of Nephrology, University of Utah School of Medicine, Salt Lake City, Utah, 84132, USA

    Wayne A. Border, Nancy A. Noble & Tatsuo Yamamoto

  2. Telios Pharmaceuticals Inc., San Diego, California, 92121, USA

    John R. Harper & Michael D. Pierschbacher

  3. Cancer Research Center, La Jolla Cancer Research Foundation, La Jolla, California, 92037, USA

    Yu Yamaguchi, Michael D. Pierschbacher & Erkki Ruoslahti

Authors
  1. Wayne A. Border
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  2. Nancy A. Noble
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  3. Tatsuo Yamamoto
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  4. John R. Harper
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  5. Yu Yamaguchi
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  6. Michael D. Pierschbacher
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  7. Erkki Ruoslahti
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Border, W., Noble, N., Yamamoto, T. et al. Natural inhibitor of transforming growth factor-β protects against scarring in experimental kidney disease. Nature 360, 361–364 (1992). https://doi.org/10.1038/360361a0

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