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. 1987 Oct 15;247(2):385–388. doi: 10.1042/bj2470385

Epidermal growth factor increases collagen production in granulation tissue by stimulation of fibroblast proliferation and not by activation of procollagen genes.

M Laato 1, V M Kähäri 1, J Niinikoski 1, E Vuorio 1
PMCID: PMC1148420  PMID: 3501286

Abstract

The effects of epidermal growth factor (EGF) on granulation-tissue formation and collagen-gene expression were studied in experimental sponge-induced granulomas in rats. After daily administration of 5 micrograms of EGF into the sponge, total RNA was extracted from the ingrown granulation tissue at days 4 and 7 and analysed by Northern hybridization for the contents of mRNAs for types I and III procollagens. EGF treatment increased procollagen mRNA, particularly at day 4. To determine whether this elevation was due to increased proliferation of collagen-producing fibroblasts or to activation of collagen-gene expression in these cells, fibroblast cultures were started from granulation tissue and treated with EGF. These experiments confirmed that EGF is a potent mitogen for granuloma fibroblasts in a dose-dependent manner. The effect of EGF treatment on radioactive hydroxyproline production in cultured cells was inhibitory. The decreased rate of collagen synthesis was also indicated by decreased amounts of procollagen mRNAs. The results suggest that the stimulation of wound healing and collagen production by EGF is due to increased fibroblast proliferation, and not to increased expression of type I and III procollagen genes.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. 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]
  2. Carpenter G., Zendegui J. G. Epidermal growth factor, its receptor, and related proteins. Exp Cell Res. 1986 May;164(1):1–10. doi: 10.1016/0014-4827(86)90449-0. [DOI] [PubMed] [Google Scholar]
  3. Franklin J. D., Lynch J. B. Effects of topical applications of epidermal growth factor on wound healing. Experimental study on rabbit ears. Plast Reconstr Surg. 1979 Dec;64(6):766–770. doi: 10.1097/00006534-197912000-00003. [DOI] [PubMed] [Google Scholar]
  4. Genovese C., Rowe D., Kream B. Construction of DNA sequences complementary to rat alpha 1 and alpha 2 collagen mRNA and their use in studying the regulation of type I collagen synthesis by 1,25-dihydroxyvitamin D. Biochemistry. 1984 Dec 4;23(25):6210–6216. doi: 10.1021/bi00320a049. [DOI] [PubMed] [Google Scholar]
  5. Jalkanen M. Connective tissue activating macromolecules in macrophage culture medium. Connect Tissue Res. 1981;9(1):19–24. doi: 10.3109/03008208109160236. [DOI] [PubMed] [Google Scholar]
  6. Juva K., Prockop D. J. Modified procedure for the assay of H-3-or C-14-labeled hydroxyproline. Anal Biochem. 1966 Apr;15(1):77–83. doi: 10.1016/0003-2697(66)90249-1. [DOI] [PubMed] [Google Scholar]
  7. Laato M. Effect of epidermal growth factor (EGF) on blood flow and albumin extravasation in experimental granulation tissue. Acta Chir Scand. 1986 Jun-Jul;152:401–405. [PubMed] [Google Scholar]
  8. Laato M., Niinikoski J., Lebel L., Gerdin B. Stimulation of wound healing by epidermal growth factor. A dose-dependent effect. Ann Surg. 1986 Apr;203(4):379–381. doi: 10.1097/00000658-198604000-00007. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Laato M., Niinikoski J., Lundberg C., Arfors K. E. Effect of epidermal growth factor (EGF) on experimental granulation tissue. J Surg Res. 1986 Sep;41(3):252–255. doi: 10.1016/0022-4804(86)90032-6. [DOI] [PubMed] [Google Scholar]
  10. Lampiaho K., Kulonen E. Metabolic phases during the development of granulation tissue. Biochem J. 1967 Oct;105(1):333–341. doi: 10.1042/bj1050333. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Miskulin M., Dalgleish R., Kluve-Beckerman B., Rennard S. I., Tolstoshev P., Brantly M., Crystal R. G. Human type III collagen gene expression is coordinately modulated with the type I collagen genes during fibroblast growth. Biochemistry. 1986 Mar 25;25(6):1408–1413. doi: 10.1021/bi00354a033. [DOI] [PubMed] [Google Scholar]
  12. Mäkelä J. K., Vuorio E. Type I collagen messenger RNA levels in experimental granulation tissue and silicosis in rats. Med Biol. 1986;64(1):15–22. [PubMed] [Google Scholar]
  13. Niall M., Ryan G. B., O'Brien B. M. The effect of epidermal growth factor on wound healing in mice. J Surg Res. 1982 Aug;33(2):164–169. doi: 10.1016/0022-4804(82)90024-5. [DOI] [PubMed] [Google Scholar]
  14. Ninikoski J., Heughan C., Hunt T. K. Oxygen and carbon dioxide tensions in experimental wounds. Surg Gynecol Obstet. 1971 Dec;133(6):1003–1007. [PubMed] [Google Scholar]
  15. 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]
  16. Rowe D. W., Moen R. C., Davidson J. M., Byers P. H., Bornstein P., Palmiter R. D. Correlation of procollagen mRNA levels in normal and transformed chick embryo fibroblasts with different rates of procollagen synthesis. Biochemistry. 1978 May 2;17(9):1581–1590. doi: 10.1021/bi00602a001. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. Thomas P. S. Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5201–5205. doi: 10.1073/pnas.77.9.5201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. White B. A., Bancroft F. C. Cytoplasmic dot hybridization. Simple analysis of relative mRNA levels in multiple small cell or tissue samples. J Biol Chem. 1982 Aug 10;257(15):8569–8572. [PubMed] [Google Scholar]

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