Skip to main content
PMC home page
The Journal of Cell Biology logoLink to The Journal of Cell Biology
. 1991 Aug 1;114(3):585–595. doi: 10.1083/jcb.114.3.585

Induced expression of syndecan in healing wounds

PMCID: PMC2289093  PMID: 1860887

Abstract

We have studied the expression of an integral cell surface proteoglycan, syndecan, during the healing of cutaneous wounds, using immunohistochemical and in situ hybridization methods. In normal mouse skin, both syndecan antigen and mRNA were found to be expressed exclusively by epidermal and hair follicle cells. After incision and subsequent suturing, remarkably increased amounts of syndecan on the cell surfaces of migrating and proliferating epidermal cells and on hair follicle cells adjacent to wound margins were noted. This increased syndecan expression was shown to be a consequence of greater amounts of syndecan mRNA. Induction was observed already 1 d after wounding, was most significant at the time of intense cell proliferation, and was still observable 14 d after incision. The migrating cells of the leading edge of the epithelium also showed enhanced syndecan expression, although clearly less than that seen in the proliferating epithelium. The merging epithelial cells at the site of incision showed little or no syndecan expression; increased syndecan expression, however, was detected during later epithelial stratification. When wounds were left unsutured, in situ hybridization experiments also revealed scattered syndecan-positive signals in the granulation tissue near the migrating epidermal sheet. By immunohistochemical analysis, positive staining in granulation tissue was observed around vascular endothelial cells in a subpopulation of growing capillaries. Induction of syndecan in granulation tissue both at the protein and mRNA levels was temporally and spatially highly restricted. Granulation tissue, which formed in viscose cellulose sponge cylinders placed under the skin of rats, was also found to produce 3.4 and 2.6 kb mRNA species of syndecan similar to that observed in the normal murine mammary epithelial cell line, NMuMG. These results suggest that syndecan may have a unique and important role as a cell adhesion and a growth factor-binding molecule not only during embryogenesis but also during tissue regeneration in mature tissues.

Full Text

The Full Text of this article is available as a PDF (1.8 MB).

Selected References

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

  1. Albelda S. M., Buck C. A. Integrins and other cell adhesion molecules. FASEB J. 1990 Aug;4(11):2868–2880. [PubMed] [Google Scholar]
  2. Burgess W. H., Maciag T. The heparin-binding (fibroblast) growth factor family of proteins. Annu Rev Biochem. 1989;58:575–606. doi: 10.1146/annurev.bi.58.070189.003043. [DOI] [PubMed] [Google Scholar]
  3. 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]
  4. Clark R. A. Fibronectin matrix deposition and fibronectin receptor expression in healing and normal skin. J Invest Dermatol. 1990 Jun;94(6 Suppl):128S–134S. doi: 10.1111/1523-1747.ep12876104. [DOI] [PubMed] [Google Scholar]
  5. Clark R. A. Potential roles of fibronectin in cutaneous wound repair. Arch Dermatol. 1988 Feb;124(2):201–206. [PubMed] [Google Scholar]
  6. Clark R. A. Wound repair. Curr Opin Cell Biol. 1989 Oct;1(5):1000–1008. doi: 10.1016/0955-0674(89)90072-0. [DOI] [PubMed] [Google Scholar]
  7. De Luca M., Tamura R. N., Kajiji S., Bondanza S., Rossino P., Cancedda R., Marchisio P. C., Quaranta V. Polarized integrin mediates human keratinocyte adhesion to basal lamina. Proc Natl Acad Sci U S A. 1990 Sep;87(17):6888–6892. doi: 10.1073/pnas.87.17.6888. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dunlap M. K., Donaldson D. J. Inability of colchicine to inhibit newt epidermal cell migration or prevent concanavalin A-mediated inhibition of migration. Studies in vivo. Exp Cell Res. 1978 Oct 1;116(1):15–19. doi: 10.1016/0014-4827(78)90059-9. [DOI] [PubMed] [Google Scholar]
  9. Edelman G. M. Morphoregulatory molecules. Biochemistry. 1988 May 17;27(10):3533–3543. doi: 10.1021/bi00410a001. [DOI] [PubMed] [Google Scholar]
  10. Elenius K., Salmivirta M., Inki P., Mali M., Jalkanen M. Binding of human syndecan to extracellular matrix proteins. J Biol Chem. 1990 Oct 15;265(29):17837–17843. [PubMed] [Google Scholar]
  11. Ffrench-Constant C., Van de Water L., Dvorak H. F., Hynes R. O. Reappearance of an embryonic pattern of fibronectin splicing during wound healing in the adult rat. J Cell Biol. 1989 Aug;109(2):903–914. doi: 10.1083/jcb.109.2.903. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Folkman J., Klagsbrun M. Angiogenic factors. Science. 1987 Jan 23;235(4787):442–447. doi: 10.1126/science.2432664. [DOI] [PubMed] [Google Scholar]
  13. Fujikawa L. S., Foster C. S., Gipson I. K., Colvin R. B. Basement membrane components in healing rabbit corneal epithelial wounds: immunofluorescence and ultrastructural studies. J Cell Biol. 1984 Jan;98(1):128–138. doi: 10.1083/jcb.98.1.128. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Gallatin W. M., Weissman I. L., Butcher E. C. A cell-surface molecule involved in organ-specific homing of lymphocytes. Nature. 1983 Jul 7;304(5921):30–34. doi: 10.1038/304030a0. [DOI] [PubMed] [Google Scholar]
  15. Gipson I. K., Westcott M. J., Brooksby N. G. Effects of cytochalasins B and D and colchicine on migration of the corneal epithelium. Invest Ophthalmol Vis Sci. 1982 May;22(5):633–642. [PubMed] [Google Scholar]
  16. Grøndahl-Hansen J., Lund L. R., Ralfkiaer E., Ottevanger V., Danø K. Urokinase- and tissue-type plasminogen activators in keratinocytes during wound reepithelialization in vivo. J Invest Dermatol. 1988 Jun;90(6):790–795. doi: 10.1111/1523-1747.ep12461511. [DOI] [PubMed] [Google Scholar]
  17. Hayashi K., Hayashi M., Boutin E., Cunha G. R., Bernfield M., Trelstad R. L. Hormonal modification of epithelial differentiation and expression of cell surface heparan sulfate proteoglycan in the mouse vaginal epithelium. An immunohistochemical and electron microscopic study. Lab Invest. 1988 Jan;58(1):68–76. [PubMed] [Google Scholar]
  18. Hayashi K., Hayashi M., Jalkanen M., Firestone J. H., Trelstad R. L., Bernfield M. Immunocytochemistry of cell surface heparan sulfate proteoglycan in mouse tissues. A light and electron microscopic study. J Histochem Cytochem. 1987 Oct;35(10):1079–1088. doi: 10.1177/35.10.2957423. [DOI] [PubMed] [Google Scholar]
  19. Heino J., Ignotz R. A., Hemler M. E., Crouse C., Massagué J. Regulation of cell adhesion receptors by transforming growth factor-beta. Concomitant regulation of integrins that share a common beta 1 subunit. J Biol Chem. 1989 Jan 5;264(1):380–388. [PubMed] [Google Scholar]
  20. Hsu S. M., Raine L., Fanger H. Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem. 1981 Apr;29(4):577–580. doi: 10.1177/29.4.6166661. [DOI] [PubMed] [Google Scholar]
  21. 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]
  22. Jalkanen M., Nguyen H., Rapraeger A., Kurn N., Bernfield M. Heparan sulfate proteoglycans from mouse mammary epithelial cells: localization on the cell surface with a monoclonal antibody. J Cell Biol. 1985 Sep;101(3):976–984. doi: 10.1083/jcb.101.3.976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Jalkanen M., Rapraeger A., Bernfield M. Mouse mammary epithelial cells produce basement membrane and cell surface heparan sulfate proteoglycans containing distinct core proteins. J Cell Biol. 1988 Mar;106(3):953–962. doi: 10.1083/jcb.106.3.953. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Jalkanen M., Rapraeger A., Saunders S., Bernfield M. Cell surface proteoglycan of mouse mammary epithelial cells is shed by cleavage of its matrix-binding ectodomain from its membrane-associated domain. J Cell Biol. 1987 Dec;105(6 Pt 2):3087–3096. doi: 10.1083/jcb.105.6.3087. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Kiefer M. C., Stephans J. C., Crawford K., Okino K., Barr P. J. Ligand-affinity cloning and structure of a cell surface heparan sulfate proteoglycan that binds basic fibroblast growth factor. Proc Natl Acad Sci U S A. 1990 Sep;87(18):6985–6989. doi: 10.1073/pnas.87.18.6985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Kinsella M. G., Wight T. N. Modulation of sulfated proteoglycan synthesis by bovine aortic endothelial cells during migration. J Cell Biol. 1986 Mar;102(3):679–687. doi: 10.1083/jcb.102.3.679. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Koda J. E., Rapraeger A., Bernfield M. Heparan sulfate proteoglycans from mouse mammary epithelial cells. Cell surface proteoglycan as a receptor for interstitial collagens. J Biol Chem. 1985 Jul 5;260(13):8157–8162. [PubMed] [Google Scholar]
  28. Larjava H., Peltonen J., Akiyama S. K., Yamada S. S., Gralnick H. R., Uitto J., Yamada K. M. Novel function for beta 1 integrins in keratinocyte cell-cell interactions. J Cell Biol. 1990 Mar;110(3):803–815. doi: 10.1083/jcb.110.3.803. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Leppä S., Härkönen P., Jalkanen M. Steroid-induced epithelial-fibroblastic conversion associated with syndecan suppression in S115 mouse mammary tumor cells. Cell Regul. 1991 Jan;2(1):1–11. doi: 10.1091/mbc.2.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Mackie E. J., Halfter W., Liverani D. Induction of tenascin in healing wounds. J Cell Biol. 1988 Dec;107(6 Pt 2):2757–2767. doi: 10.1083/jcb.107.6.2757. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Mali M., Jaakkola P., Arvilommi A. M., Jalkanen M. Sequence of human syndecan indicates a novel gene family of integral membrane proteoglycans. J Biol Chem. 1990 Apr 25;265(12):6884–6889. [PubMed] [Google Scholar]
  32. Maples J. A. A method for the covalent attachment of cells to glass slides for use in immunohistochemical assays. Am J Clin Pathol. 1985 Mar;83(3):356–363. doi: 10.1093/ajcp/83.3.356. [DOI] [PubMed] [Google Scholar]
  33. 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]
  34. 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]
  35. Rapraeger A., Jalkanen M., Bernfield M. Cell surface proteoglycan associates with the cytoskeleton at the basolateral cell surface of mouse mammary epithelial cells. J Cell Biol. 1986 Dec;103(6 Pt 2):2683–2696. doi: 10.1083/jcb.103.6.2683. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Rapraeger A., Jalkanen M., Endo E., Koda J., Bernfield M. The cell surface proteoglycan from mouse mammary epithelial cells bears chondroitin sulfate and heparan sulfate glycosaminoglycans. J Biol Chem. 1985 Sep 15;260(20):11046–11052. [PubMed] [Google Scholar]
  37. Ruoslahti E., Pierschbacher M. D. New perspectives in cell adhesion: RGD and integrins. Science. 1987 Oct 23;238(4826):491–497. doi: 10.1126/science.2821619. [DOI] [PubMed] [Google Scholar]
  38. Ruoslahti E. Proteoglycans in cell regulation. J Biol Chem. 1989 Aug 15;264(23):13369–13372. [PubMed] [Google Scholar]
  39. Ruoslahti E., Yamaguchi Y. Proteoglycans as modulators of growth factor activities. Cell. 1991 Mar 8;64(5):867–869. doi: 10.1016/0092-8674(91)90308-l. [DOI] [PubMed] [Google Scholar]
  40. Salmivirta M., Elenius K., Vainio S., Hofer U., Chiquet-Ehrismann R., Thesleff I., Jalkanen M. Syndecan from embryonic tooth mesenchyme binds tenascin. J Biol Chem. 1991 Apr 25;266(12):7733–7739. [PubMed] [Google Scholar]
  41. Sanderson R. D., Bernfield M. Molecular polymorphism of a cell surface proteoglycan: distinct structures on simple and stratified epithelia. Proc Natl Acad Sci U S A. 1988 Dec;85(24):9562–9566. doi: 10.1073/pnas.85.24.9562. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Saunders S., Bernfield M. Cell surface proteoglycan binds mouse mammary epithelial cells to fibronectin and behaves as a receptor for interstitial matrix. J Cell Biol. 1988 Feb;106(2):423–430. doi: 10.1083/jcb.106.2.423. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Saunders S., Jalkanen M., O'Farrell S., Bernfield M. Molecular cloning of syndecan, an integral membrane proteoglycan. J Cell Biol. 1989 Apr;108(4):1547–1556. doi: 10.1083/jcb.108.4.1547. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Solursh M., Reiter R. S., Jensen K. L., Kato M., Bernfield M. Transient expression of a cell surface heparan sulfate proteoglycan (syndecan) during limb development. Dev Biol. 1990 Jul;140(1):83–92. doi: 10.1016/0012-1606(90)90055-n. [DOI] [PubMed] [Google Scholar]
  45. Stanley J. R., Alvarez O. M., Bere E. W., Jr, Eaglstein W. H., Katz S. I. Detection of basement membrane zone antigens during epidermal wound healing in pigs. J Invest Dermatol. 1981 Aug;77(2):240–243. doi: 10.1111/1523-1747.ep12480082. [DOI] [PubMed] [Google Scholar]
  46. Stenn K. S., Madri J. A., Roll F. J. Migrating epidermis produces AB2 collagen and requires continual collagen synthesis for movement. Nature. 1979 Jan 18;277(5693):229–232. doi: 10.1038/277229a0. [DOI] [PubMed] [Google Scholar]
  47. Sun X., Mosher D. F., Rapraeger A. Heparan sulfate-mediated binding of epithelial cell surface proteoglycan to thrombospondin. J Biol Chem. 1989 Feb 15;264(5):2885–2889. [PubMed] [Google Scholar]
  48. Takeichi M. Cadherins: a molecular family important in selective cell-cell adhesion. Annu Rev Biochem. 1990;59:237–252. doi: 10.1146/annurev.bi.59.070190.001321. [DOI] [PubMed] [Google Scholar]
  49. Thesleff I., Jalkanen M., Vainio S., Bernfield M. Cell surface proteoglycan expression correlates with epithelial-mesenchymal interaction during tooth morphogenesis. Dev Biol. 1988 Oct;129(2):565–572. doi: 10.1016/0012-1606(88)90401-0. [DOI] [PubMed] [Google Scholar]
  50. VILJANTO J., KIVIKOSKI A. The local effect of neutral salt-soluble collagen on the formation of granulation tissue. Ann Med Exp Biol Fenn. 1962;40:118–127. [PubMed] [Google Scholar]
  51. Vainio S., Jalkanen M., Thesleff I. Syndecan and tenascin expression is induced by epithelial-mesenchymal interactions in embryonic tooth mesenchyme. J Cell Biol. 1989 May;108(5):1945–1953. doi: 10.1083/jcb.108.5.1945. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Vainio S., Lehtonen E., Jalkanen M., Bernfield M., Saxén L. Epithelial-mesenchymal interactions regulate the stage-specific expression of a cell surface proteoglycan, syndecan, in the developing kidney. Dev Biol. 1989 Aug;134(2):382–391. doi: 10.1016/0012-1606(89)90110-3. [DOI] [PubMed] [Google Scholar]
  53. Wilkinson D. G., Bhatt S., McMahon A. P. Expression pattern of the FGF-related proto-oncogene int-2 suggests multiple roles in fetal development. Development. 1989 Jan;105(1):131–136. doi: 10.1242/dev.105.1.131. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Cell Biology are provided here courtesy of The Rockefeller University Press

RESOURCES