Detection of TGFβ in Body Fluids and Tissues

  • Andrew H. Limper
Part of the Methods in Molecular Biology™ book series (MIMB, volume 142)


Transforming growth factor-β1 (TGF-(β1) is a 25-kDa homodimeric protein secreted by numerous cells including platelets, monocytes, macrophages, epithelial cells, and fibroblasts (1, 2, 3). Active TGF-(β1 exerts multiple and divergent effects on mesenchymal and epithelial cell cycle regulation (1). In addition, TGF-(β1 influences the expression of multiple genes, which act in concert to enhance the synthesis of extracellular matrix components with resulting fibrosis (1,2). In vitro studies have demonstrated that TGF-(β1 regulates the genetic expression of extracellular matrix components, including fibronectin (FN), the α5β1 fibronectin receptor (FNR), collagen, and proteoglycans (4, 5, 6, 7).


Idiopathic Pulmonary Fibrosis Extracellular Matrix Component Pulmonary Sarcoidosis Methylene Green Body Fluid Sample 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Sporn M. B. and Roberts A. B. (1988) Peptide growth factors are multifunctional. Nature 332, 217–219.PubMedCrossRefGoogle Scholar
  2. 2.
    Roberts A. B. and Sporn M.B. (1990) The transforming growth factor betas,in Peptide Growth Factors and Their Receptors. Handbook of Experimental Pharmacology (Sporn M. B. and Roberts A. B. eds.), Springer-Verlag, Berlin, Vol. 95/1, pp. 419–472.Google Scholar
  3. 3.
    Sporn M. B. Roberts A. B. Wakefield L. M., and de Crombrugghe B. (1987) Some recent advances in the chemistry and biology of transforming growth factor beta. J. Cell Biol. 105, 1039–1045.PubMedCrossRefGoogle Scholar
  4. 4.
    Roberts C. J., Birkenmeier T. M., McQuillan J. J., Akiyama S. K., Yamada S. S., Chen W. T., Yamada K. M., and McDonald J. A. Transforming growth factor-β stimulates the expression of fibronectin and both subunits of the human fibronectin receptor by cultured human lung fibroblasts. J. Biol. Chem. 263, 4586–4592.Google Scholar
  5. 5.
    Ignotz R. A. and Massague J. (1986) Transforming growth factor beta stimulates the expression of fibronectin and collagen and their incorporation into the extracellular matrix. J. Biol. Chem. 261, 4337–4345.PubMedGoogle Scholar
  6. 6.
    Roberts A. B., Sporn M. B., and Assoian R. K. (1986) Transforming growth factor type beta: rapid induction of fibrosis in vivo and stimulation of collagen formation in vitro. Proc. Natl. Acad. Sci. USA 83, 4167–4171.PubMedCrossRefGoogle Scholar
  7. 7.
    Westergren-Thorssen G., Schmidtchen A., Sarnstrand B., and Fransson L. A. TGF-β induces selective increase of proteoglycan production and changes in the copolymer structure of dermatan sulfate in human skin fibroblasts. Eur. J. Biochem. 205, 277–286.Google Scholar
  8. 8.
    Border W. A. and Noble N. A. (1994) Transforming growth factor beta in tissue fibrosis. N. Engl. J. Med. 331, 1286–1292.PubMedCrossRefGoogle Scholar
  9. 9.
    Liu X., Yue J., Frey R. S., Zhu Q., and Mulder K. M. (1998) Transforming growth factor beta signaling through Smad1 in human breast cancer cells. Cancer Res. 58(20), 4752–4757.Google Scholar
  10. 10.
    Broekelmann T.J., Limper A.H., Colby T. V., and McDonald J.A. (1991) Transforming growth factor-β1 is present at sites of extracellular matrix gene expression in human pulmonary fibrosis. Proc. Natl. Acad. Sci. USA 88, 6642–6646.PubMedCrossRefGoogle Scholar
  11. 11.
    Limper A. H., Colby T. V., Sanders M. S., Asakura S., Roche P. C., and DeRemee R. A. (1994) Immuno-histochemical localization of transforming growth factor-β1 in the nonnecrotizing granulomas of pulmonary sarcoidosis. Am. J. Respir. Crit. Care. Med. 149, 197–204.PubMedGoogle Scholar
  12. 12.
    Border W. A., Noble N. A., Yamamoto T., Harper J. R., Yamaguchi Y., Pierschbacher M. D., and Ruoslahti E. (1992) Natural inhibitor of transforming growth factor-beta protects against scarring in experimental kidney disease.Nature 360, 361–36PubMedCrossRefGoogle Scholar
  13. 13.
    Limper A. H., Broekelmann T. J., Colby T. V., Malizia G., and McDonald J. A. (1991) Analysis of local mRNA for extracellular matrix proteins and growth factors using in situ hybridization in fibroproliferative lung disorders. Chest 99, 55S–56PubMedCrossRefGoogle Scholar
  14. 14.
    Khalil N., O’Connor R. N., Unruh H. W., Warren P. W., Flanders K. C., Kemp A., Bereznay A. H., and Greenberg A. H. (1991) Increased production and immunohistochemical localization of transforming growth factor-β in idiopathic pulmonary fibrosis. Am. J. Respir. CellMol. Biol. 5, 155–162.Google Scholar
  15. 15.
    Anscher M. S., Peters W. P., Reisenbichler H., Petros W. P., Pharm D., and Jirtle R. L. Transforming growth factor p as a predictor of liver and lung fibrosis after autologous bone marrow transplantation for advanced breast cancer. N. Engl. J. Med. 328, 1592–1598.Google Scholar
  16. 16.
    Yong S.-J. and Limper A. H. (1997) A cross-sectional analysis of plasma TGF-β1 during idiopathic pulmonary fibrosis (abstr). Am. J. Respir. Crit. Care Med. 155, A311.Google Scholar
  17. 17.
    Sanderson N., Factor V., Nagy P., Kopp J., Kondaiah P., Wakefield L., Roberts A. B., Sporn M. B., and Thorgeirsson S. S. (1995) Hepatic expression of mature transforming growth factor beta 1 in transgenic mice results in multiple tissue lesions. Proc. Natl. Acad. Sci. USA 92, 2572–2576.PubMedCrossRefGoogle Scholar
  18. 18.
    Deguchi Y. (1992) Spontaneous increase of transforming growth factor β production by broncho-alveolar mononuclear cells of patients with systemic autoimmune diseases affecting the lung. Ann. Rheum. Dis. 51, 362–365.PubMedCrossRefGoogle Scholar
  19. 19.
    Denis M. and Ghadirian E. Transforming growth factor p is generated in the course of hypersensitivity pneumonitis: contribution to collagen synthesis. Am. J. Respir. Cell Mol. Biol. 7, 156–160.Google Scholar
  20. 20.
    Adlakha A, Standing J. E., and Limper A. H. (1994) Elevated levels of TGF-β in serum of patients with idiopathic pulmonary fibrosis (abstr). Chest 106, 60Google Scholar
  21. 21.
    Asakura S., Colby T. V., and Limper A. H. (1996) Tissue localization of transforming rowth factor-β1 in pulmonary eosinophilic granuloma. Am. J. Respir. Crit. Care Med. 154, 1525–153PubMedGoogle Scholar
  22. 22.
    Flanders K. C., Thompson N. L., Cissel D. S., Ellingsworth D. R., Roberts A. B., and Sporn M.B. (1989) Transforming growth factor-⨿1: histochemical localization with antibodies to different epitopes. J. Cell. Biol. 108, 653–660.PubMedCrossRefGoogle Scholar
  23. 23.
    Ellingsworth L. R., Brennan J. E., Fok K., Roberts A. B., and Sporn M. B. (1989) Antibodies to the N-terminal portion cartilage-inducing factor-A and transforming growth factor-β1. J. Biol. Chem. 261, 12,362–12,367.Google Scholar
  24. 24.
    Danielpour D., Dart L. L., Flanders K. C., Roberts A. B., and Sporn M.B. (1989) Immunodetection and quantitation of the two forms of transforming growth factor-beta (TGF-beta 1 and TGF-beta 2) secreted by cells in culture. J. Cell Physiol. 138, 79–86.PubMedCrossRefGoogle Scholar
  25. 25.
    Derynck R., Jarrett J. A., Chen E. Y., Eaton D. H., Bell J. R., Assoian R. K., Roberts A. B., Sporn M. B., and Goeddel D. V. (1995) Human transforming growth factor-beta complementary DNA sequence and expression in normal and transformed cells. Nature 316, 701–705.CrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 2000

Authors and Affiliations

  • Andrew H. Limper
    • 1
  1. 1.Department of MedicineBiochemistry and Molecular Biology, Mayo ClinicRochester

Personalised recommendations