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. 1988 Jul;85(13):4894–4897. doi: 10.1073/pnas.85.13.4894

Transforming growth factor beta stimulates collagen-matrix contraction by fibroblasts: implications for wound healing.

R Montesano 1, L Orci 1
PMCID: PMC280543  PMID: 3164478

Abstract

An important event during wound healing is the contraction of newly formed connective tissue (granulation tissue) by fibroblasts. The role of polypeptide growth factors in the process of wound contraction was investigated by analyzing the influence of transforming growth factor beta (TGF-beta), platelet-derived growth factor on the ability of fibroblasts to contract a collagen matrix in an in vitro system. TGF-beta, but not the other growth factors tested, markedly enhanced the ability of BHK-21,3T3-L1, and human foreskin fibroblasts to contract collagen gels. These results suggest that TGF-beta released from platelets and inflammatory cells at sites of tissue injury stimulates fibroblasts to contract the provisional wound matrix and that this effect contributes to the ability of TGF-beta to accelerate wound healing.

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Selected References

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  1. Allen T. D., Schor S. L. The contraction of collagen matrices by dermal fibroblasts. J Ultrastruct Res. 1983 May;83(2):205–219. doi: 10.1016/s0022-5320(83)90078-3. [DOI] [PubMed] [Google Scholar]
  2. Assoian R. K., Fleurdelys B. E., Stevenson H. C., Miller P. J., Madtes D. K., Raines E. W., Ross R., Sporn M. B. Expression and secretion of type beta transforming growth factor by activated human macrophages. Proc Natl Acad Sci U S A. 1987 Sep;84(17):6020–6024. doi: 10.1073/pnas.84.17.6020. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Assoian R. K., Sporn M. B. Type beta transforming growth factor in human platelets: release during platelet degranulation and action on vascular smooth muscle cells. J Cell Biol. 1986 Apr;102(4):1217–1223. doi: 10.1083/jcb.102.4.1217. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bell E., Ivarsson B., Merrill C. Production of a tissue-like structure by contraction of collagen lattices by human fibroblasts of different proliferative potential in vitro. Proc Natl Acad Sci U S A. 1979 Mar;76(3):1274–1278. doi: 10.1073/pnas.76.3.1274. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bellows C. G., Melcher A. H., Aubin J. E. Contraction and organization of collagen gels by cells cultured from periodontal ligament, gingiva and bone suggest functional differences between cell types. J Cell Sci. 1981 Aug;50:299–314. doi: 10.1242/jcs.50.1.299. [DOI] [PubMed] [Google Scholar]
  6. Buckley A., Davidson J. M., Kamerath C. D., Wolt T. B., Woodward S. C. Sustained release of epidermal growth factor accelerates wound repair. Proc Natl Acad Sci U S A. 1985 Nov;82(21):7340–7344. doi: 10.1073/pnas.82.21.7340. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Ehrlich H. P., Wyler D. J. Fibroblast contraction of collagen lattices in vitro: inhibition by chronic inflammatory cell mediators. J Cell Physiol. 1983 Sep;116(3):345–351. doi: 10.1002/jcp.1041160312. [DOI] [PubMed] [Google Scholar]
  8. Gabbiani G., Hirschel B. J., Ryan G. B., Statkov P. R., Majno G. Granulation tissue as a contractile organ. A study of structure and function. J Exp Med. 1972 Apr 1;135(4):719–734. doi: 10.1084/jem.135.4.719. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Ignotz R. A., Massagué J. Cell adhesion protein receptors as targets for transforming growth factor-beta action. Cell. 1987 Oct 23;51(2):189–197. doi: 10.1016/0092-8674(87)90146-2. [DOI] [PubMed] [Google Scholar]
  10. Ignotz R. A., Massagué J. Transforming growth factor-beta stimulates the expression of fibronectin and collagen and their incorporation into the extracellular matrix. J Biol Chem. 1986 Mar 25;261(9):4337–4345. [PubMed] [Google Scholar]
  11. Kehrl J. H., Wakefield L. M., Roberts A. B., Jakowlew S., Alvarez-Mon M., Derynck R., Sporn M. B., Fauci A. S. Production of transforming growth factor beta by human T lymphocytes and its potential role in the regulation of T cell growth. J Exp Med. 1986 May 1;163(5):1037–1050. doi: 10.1084/jem.163.5.1037. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Leof E. B., Proper J. A., Getz M. J., Moses H. L. Transforming growth factor type beta regulation of actin mRNA. J Cell Physiol. 1986 Apr;127(1):83–88. doi: 10.1002/jcp.1041270111. [DOI] [PubMed] [Google Scholar]
  13. Lynch S. E., Nixon J. C., Colvin R. B., Antoniades H. N. Role of platelet-derived growth factor in wound healing: synergistic effects with other growth factors. Proc Natl Acad Sci U S A. 1987 Nov;84(21):7696–7700. doi: 10.1073/pnas.84.21.7696. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Montandon D., Gabbiani G., Ryan G. B., Majno G. The contractile fibroblast. Its relevance in plastic surgery. Plast Reconstr Surg. 1973 Sep;52(3):286–290. [PubMed] [Google Scholar]
  15. Montesano R., Orci L. Tumor-promoting phorbol esters induce angiogenesis in vitro. Cell. 1985 Sep;42(2):469–477. doi: 10.1016/0092-8674(85)90104-7. [DOI] [PubMed] [Google Scholar]
  16. Mustoe T. A., Pierce G. F., Thomason A., Gramates P., Sporn M. B., Deuel T. F. Accelerated healing of incisional wounds in rats induced by transforming growth factor-beta. Science. 1987 Sep 11;237(4820):1333–1336. doi: 10.1126/science.2442813. [DOI] [PubMed] [Google Scholar]
  17. Postlethwaite A. E., Keski-Oja J., Moses H. L., Kang A. H. Stimulation of the chemotactic migration of human fibroblasts by transforming growth factor beta. J Exp Med. 1987 Jan 1;165(1):251–256. doi: 10.1084/jem.165.1.251. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Raghow R., Postlethwaite A. E., Keski-Oja J., Moses H. L., Kang A. H. Transforming growth factor-beta increases steady state levels of type I procollagen and fibronectin messenger RNAs posttranscriptionally in cultured human dermal fibroblasts. J Clin Invest. 1987 Apr;79(4):1285–1288. doi: 10.1172/JCI112950. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Roberts A. B., Sporn M. B., Assoian R. K., Smith J. M., Roche N. S., Wakefield L. M., Heine U. I., Liotta L. A., Falanga V., Kehrl J. H. Transforming growth factor type beta: rapid induction of fibrosis and angiogenesis in vivo and stimulation of collagen formation in vitro. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4167–4171. doi: 10.1073/pnas.83.12.4167. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Ross R. The fibroblast and wound repair. Biol Rev Camb Philos Soc. 1968 Feb;43(1):51–96. doi: 10.1111/j.1469-185x.1968.tb01109.x. [DOI] [PubMed] [Google Scholar]
  21. Schultz G. S., White M., Mitchell R., Brown G., Lynch J., Twardzik D. R., Todaro G. J. Epithelial wound healing enhanced by transforming growth factor-alpha and vaccinia growth factor. Science. 1987 Jan 16;235(4786):350–352. doi: 10.1126/science.3492044. [DOI] [PubMed] [Google Scholar]
  22. Sporn M. B., Roberts A. B. Peptide growth factors and inflammation, tissue repair, and cancer. J Clin Invest. 1986 Aug;78(2):329–332. doi: 10.1172/JCI112580. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Sporn M. B., Roberts A. B., Shull J. H., Smith J. M., Ward J. M., Sodek J. Polypeptide transforming growth factors isolated from bovine sources and used for wound healing in vivo. Science. 1983 Mar 18;219(4590):1329–1331. doi: 10.1126/science.6572416. [DOI] [PubMed] [Google Scholar]
  24. Sporn M. B., Roberts A. B., Wakefield L. M., de Crombrugghe B. Some recent advances in the chemistry and biology of transforming growth factor-beta. J Cell Biol. 1987 Sep;105(3):1039–1045. doi: 10.1083/jcb.105.3.1039. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Steinberg B. M., Smith K., Colozzo M., Pollack R. Establishment and transformation diminish the ability of fibroblasts to contract a native collagen gel. J Cell Biol. 1980 Oct;87(1):304–308. doi: 10.1083/jcb.87.1.304. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Stopak D., Harris A. K. Connective tissue morphogenesis by fibroblast traction. I. Tissue culture observations. Dev Biol. 1982 Apr;90(2):383–398. doi: 10.1016/0012-1606(82)90388-8. [DOI] [PubMed] [Google Scholar]
  27. Varga J., Rosenbloom J., Jimenez S. A. Transforming growth factor beta (TGF beta) causes a persistent increase in steady-state amounts of type I and type III collagen and fibronectin mRNAs in normal human dermal fibroblasts. Biochem J. 1987 Nov 1;247(3):597–604. doi: 10.1042/bj2470597. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Wahl S. M., Hunt D. A., Wakefield L. M., McCartney-Francis N., Wahl L. M., Roberts A. B., Sporn M. B. Transforming growth factor type beta induces monocyte chemotaxis and growth factor production. Proc Natl Acad Sci U S A. 1987 Aug;84(16):5788–5792. doi: 10.1073/pnas.84.16.5788. [DOI] [PMC free article] [PubMed] [Google Scholar]

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