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. 1989 Apr;9(4):1642–1650. doi: 10.1128/mcb.9.4.1642

Fibronectin is overproduced by keloid fibroblasts during abnormal wound healing.

M Babu 1, R Diegelmann 1, N Oliver 1
PMCID: PMC362582  PMID: 2524650

Abstract

Wound healing in certain individuals leads to the development of keloid tumors which exhibit abnormal collagen metabolism and an increased abundance of extracellular matrix components. Comparison of fibronectin levels in fibroblasts derived from keloids and normal dermis revealed a relative increase in intracellular and extracellular fibronectin in the keloid-derived cells. While fibronectin was similarly processed, compartmentalized, and degraded by both cell types, fibronectin biosynthesis was found to be accelerated as much as fourfold in keloid fibroblasts due to a corresponding increase in the amount of accumulated fibronectin mRNA. These changes account for the elevated steady-state level of the molecule in keloid fibroblasts and suggest that increased fibronectin in keloid lesions is due to overproduction by the wound-healing fibroblasts. Glucocorticoid treatment stimulated fibronectin biosynthesis in both normal and keloid fibroblasts. However, the amount of stimulation was less for the keloid-derived cells, indicating a limitation on maximal rates of fibronectin biosynthesis. These observations suggest that separate mechanisms act to control basal and maximal rates of fibronectin production. Biosynthesis of the 140-kilodalton fibronectin receptor was also found to be increased in keloid fibroblasts, suggesting some level of coordinate regulation for fibronectin and fibronectin receptor expression.

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Selected References

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

  1. Abergel R. P., Chu M. L., Bauer E. A., Uitto J. Regulation of collagen gene expression in cutaneous diseases with dermal fibrosis: evidence for pretranslational control. J Invest Dermatol. 1987 Jun;88(6):727–731. doi: 10.1111/1523-1747.ep12470397. [DOI] [PubMed] [Google Scholar]
  2. Abergel R. P., Pizzurro D., Meeker C. A., Lask G., Matsuoka L. Y., Minor R. R., Chu M. L., Uitto J. Biochemical composition of the connective tissue in keloids and analysis of collagen metabolism in keloid fibroblast cultures. J Invest Dermatol. 1985 May;84(5):384–390. doi: 10.1111/1523-1747.ep12265471. [DOI] [PubMed] [Google Scholar]
  3. Askey D. B., Herman I. M. Computer-assisted analysis of the vascular endothelial cell motile response to injury. Comput Biomed Res. 1988 Dec;21(6):551–561. doi: 10.1016/0010-4809(88)90011-0. [DOI] [PubMed] [Google Scholar]
  4. BLOOM D. Heredity of keloids; review of the literature and report of a family with multiple keloids in five generations. N Y State J Med. 1956 Feb 15;56(4):511–519. [PubMed] [Google Scholar]
  5. Chen T. R. In situ detection of mycoplasma contamination in cell cultures by fluorescent Hoechst 33258 stain. Exp Cell Res. 1977 Feb;104(2):255–262. doi: 10.1016/0014-4827(77)90089-1. [DOI] [PubMed] [Google Scholar]
  6. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  7. Clore J. N., Cohen I. K., Diegelmann R. F. Quantitative assay of types I and III collagen synthesized by keloid biopsyes and fibroblasts. Biochim Biophys Acta. 1979 Aug 22;586(2):384–390. doi: 10.1016/0304-4165(79)90107-7. [DOI] [PubMed] [Google Scholar]
  8. Diegelmann R. F., Cohen I. K., McCoy B. J. Growth kinetics and collagen synthesis of normal skin, normal scar and keloid fibroblasts in vitro. J Cell Physiol. 1979 Feb;98(2):341–346. doi: 10.1002/jcp.1040980210. [DOI] [PubMed] [Google Scholar]
  9. Grinnell F., Billingham R. E., Burgess L. Distribution of fibronectin during wound healing in vivo. J Invest Dermatol. 1981 Mar;76(3):181–189. doi: 10.1111/1523-1747.ep12525694. [DOI] [PubMed] [Google Scholar]
  10. Grinnell F. Fibronectin and wound healing. J Cell Biochem. 1984;26(2):107–116. doi: 10.1002/jcb.240260206. [DOI] [PubMed] [Google Scholar]
  11. Hynes R. O. Integrins: a family of cell surface receptors. Cell. 1987 Feb 27;48(4):549–554. doi: 10.1016/0092-8674(87)90233-9. [DOI] [PubMed] [Google Scholar]
  12. Hynes R. O., Yamada K. M. Fibronectins: multifunctional modular glycoproteins. J Cell Biol. 1982 Nov;95(2 Pt 1):369–377. doi: 10.1083/jcb.95.2.369. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hynes R. Molecular biology of fibronectin. Annu Rev Cell Biol. 1985;1:67–90. doi: 10.1146/annurev.cb.01.110185.000435. [DOI] [PubMed] [Google Scholar]
  14. James W. D., Besanceney C. D., Odom R. B. The ultrastructure of a keloid. J Am Acad Dermatol. 1980 Jul;3(1):50–57. doi: 10.1016/s0190-9622(80)80224-6. [DOI] [PubMed] [Google Scholar]
  15. Ketchum L. D., Cohen I. K., Masters F. W. Hypertrophic scars and keloids. A collective review. Plast Reconstr Surg. 1974 Feb;53(2):140–154. doi: 10.1097/00006534-197402000-00004. [DOI] [PubMed] [Google Scholar]
  16. Kischer C. W., Hendrix M. J. Fibronectin (FN) in hypertrophic scars and keloids. Cell Tissue Res. 1983;231(1):29–37. doi: 10.1007/BF00215771. [DOI] [PubMed] [Google Scholar]
  17. Kischer C. W., Shetlar M. R., Chvapil M. Hypertrophic scars and keloids: a review and new concept concerning their origin. Scan Electron Microsc. 1982;(Pt 4):1699–1713. [PubMed] [Google Scholar]
  18. Kornblihtt A. R., Vibe-Pedersen K., Baralle F. E. Human fibronectin: cell specific alternative mRNA splicing generates polypeptide chains differing in the number of internal repeats. Nucleic Acids Res. 1984 Jul 25;12(14):5853–5868. doi: 10.1093/nar/12.14.5853. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kurkinen M., Vaheri A., Roberts P. J., Stenman S. Sequential appearance of fibronectin and collagen in experimental granulation tissue. Lab Invest. 1980 Jul;43(1):47–51. [PubMed] [Google Scholar]
  20. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  21. Leptin M. The fibronectin receptor family. Nature. 1986 Jun 19;321(6072):728–728. doi: 10.1038/321728a0. [DOI] [PubMed] [Google Scholar]
  22. Linder E., Stenman S., Lehto V. P., Vaheri A. Distribution of fibronectin in human tissues and relationship to other connective tissue components. Ann N Y Acad Sci. 1978 Jun 20;312:151–159. doi: 10.1111/j.1749-6632.1978.tb16800.x. [DOI] [PubMed] [Google Scholar]
  23. Meinkoth J., Wahl G. Hybridization of nucleic acids immobilized on solid supports. Anal Biochem. 1984 May 1;138(2):267–284. doi: 10.1016/0003-2697(84)90808-x. [DOI] [PubMed] [Google Scholar]
  24. Mosher D. F. Physiology of fibronectin. Annu Rev Med. 1984;35:561–575. doi: 10.1146/annurev.me.35.020184.003021. [DOI] [PubMed] [Google Scholar]
  25. Murray J. C., Pollack S. V., Pinnell S. R. Keloids: a review. J Am Acad Dermatol. 1981 Apr;4(4):461–470. doi: 10.1016/s0190-9622(81)70048-3. [DOI] [PubMed] [Google Scholar]
  26. Oliver N. A. Altered production of fibronectin and collagen in hypercortisolism may inhibit tissue repair. Arch Dermatol. 1987 May;123(5):570–571. [PubMed] [Google Scholar]
  27. Oliver N., Newby R. F., Furcht L. T., Bourgeois S. Regulation of fibronectin biosynthesis by glucocorticoids in human fibrosarcoma cells and normal fibroblasts. Cell. 1983 May;33(1):287–296. doi: 10.1016/0092-8674(83)90357-4. [DOI] [PubMed] [Google Scholar]
  28. Oluwasanmi J. O. Keloids in the African. Clin Plast Surg. 1974 Jan;1(1):179–195. [PubMed] [Google Scholar]
  29. Omo-Dare P. Genetic studies on keloid. J Natl Med Assoc. 1975 Nov;67(6):428–432. [PMC free article] [PubMed] [Google Scholar]
  30. Pytela R., Pierschbacher M. D., Ruoslahti E. Identification and isolation of a 140 kd cell surface glycoprotein with properties expected of a fibronectin receptor. Cell. 1985 Jan;40(1):191–198. doi: 10.1016/0092-8674(85)90322-8. [DOI] [PubMed] [Google Scholar]
  31. Ramakrishnan K. M., Thomas K. P., Sundararajan C. R. Study of 1,000 patients with keloids in South India. Plast Reconstr Surg. 1974 Mar;53(3):276–280. doi: 10.1097/00006534-197403000-00004. [DOI] [PubMed] [Google Scholar]
  32. Rasheed S., Nelson-Rees W. A., Toth E. M., Arnstein P., Gardner M. B. Characterization of a newly derived human sarcoma cell line (HT-1080). Cancer. 1974 Apr;33(4):1027–1033. doi: 10.1002/1097-0142(197404)33:4<1027::aid-cncr2820330419>3.0.co;2-z. [DOI] [PubMed] [Google Scholar]
  33. Russell J. D., Witt W. S. Cell size and growth characteristics of cultured fibroblasts isolated from normal and keloid tissue. Plast Reconstr Surg. 1976 Feb;57(2):207–212. doi: 10.1097/00006534-197602000-00014. [DOI] [PubMed] [Google Scholar]
  34. Russell S. B., Trupin K. M., Rodríguez-Eaton S., Russell J. D., Trupin J. S. Reduced growth-factor requirement of keloid-derived fibroblasts may account for tumor growth. Proc Natl Acad Sci U S A. 1988 Jan;85(2):587–591. doi: 10.1073/pnas.85.2.587. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Ryan G. B., Cliff W. J., Gabbiani G., Irlé C., Montandon D., Statkov P. R., Majno G. Myofibroblasts in human granulation tissue. Hum Pathol. 1974 Jan;5(1):55–67. doi: 10.1016/s0046-8177(74)80100-0. [DOI] [PubMed] [Google Scholar]
  36. Shull S., Cutroneo K. R. Glucocorticoids coordinately regulate procollagens type I and type III synthesis. J Biol Chem. 1983 Mar 10;258(5):3364–3369. [PubMed] [Google Scholar]
  37. Sterling K. M., Jr, Harris M. J., Mitchell J. J., DiPetrillo T. A., Delaney G. L., Cutroneo K. R. Dexamethasone decreases the amounts of type I procollagen mRNAs in vivo and in fibroblast cell cultures. J Biol Chem. 1983 Jun 25;258(12):7644–7647. [PubMed] [Google Scholar]
  38. Tyagi J. S., Hirano H., Merlino G. T., Pastan I. Transcriptional control of the fibronectin gene in chick embryo fibroblasts transformed by Rous sarcoma virus. J Biol Chem. 1983 May 10;258(9):5787–5793. [PubMed] [Google Scholar]
  39. Uitto J., Murray L. W., Blumberg B., Shamban A. UCLA conference. Biochemistry of collagen in diseases. Ann Intern Med. 1986 Nov;105(5):740–756. doi: 10.7326/0003-4819-105-5-740. [DOI] [PubMed] [Google Scholar]
  40. Uitto J., Perejda A. J., Abergel R. P., Chu M. L., Ramirez F. Altered steady-state ratio of type I/III procollagen mRNAs correlates with selectively increased type I procollagen biosynthesis in cultured keloid fibroblasts. Proc Natl Acad Sci U S A. 1985 Sep;82(17):5935–5939. doi: 10.1073/pnas.82.17.5935. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Yamada K. M., Akiyama S. K., Hasegawa T., Hasegawa E., Humphries M. J., Kennedy D. W., Nagata K., Urushihara H., Olden K., Chen W. T. Recent advances in research on fibronectin and other cell attachment proteins. J Cell Biochem. 1985;28(2):79–97. doi: 10.1002/jcb.240280202. [DOI] [PubMed] [Google Scholar]

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