Skip to main content
SpringerLink
Log in

Tissue Scarring

Lessons from Wound Healing

  • Chapter
Fibrogenesis: Cellular and Molecular Basis

Part of the book series: Medical Intelligence Unit ((MIUN))

  • 419 Accesses

Abstract

Tissue scarring due to abnormal matrix remodeling is an important cause of organ failure, which is a leading cause of morbidity and mortality. Current studies have fo cused on determination of the molecular basis of controlled wound healing and uncontrolled tissue scarring. Scarless repair is a unique feature of fetal wounds in early gestation. Our understanding of the molecular basis of fetal response during wound healing may represent a paradigm to modulate incomplete and/or excessive healing (tissue scarring) to an ideal scarless healing. Once the fetal microenvironment that steers scarless wound healing is known, attempts to create a similar artificial environment to modulate abnormal tissue scarring could be accomplished. This brief review addresses the pathogenesis of wound healing and its relevance to tissue scarring.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Jameson J, Ugarte K, Chen N et al. A role for skin gammadelta T cells in wound repair. Science 2002; 296:747–749.

    Article  CAS  PubMed  Google Scholar 

  2. Marikovsky M, Breuing K, Liu PY et al. Appearance of heaparin-binding EGF-like growth factor in wound fluid as a response to injury. Proc Natl Acad Sci USA 1993; 90:3889–3893.

    Article  CAS  PubMed  Google Scholar 

  3. Seppa H, Grotendorst G, Seppa S et al. Platelet-derived growth factor in chemotactic for fibroblasts. J Cell Biol 1982; 92:584–588

    Article  CAS  PubMed  Google Scholar 

  4. Nissen NN, Polverini PJ, Koch AE et al. Vascular endothelial growth factor mediates angiogenic activity during the proliferative phase of wound healing. Am J Pathol 1998; 152:1445–1452

    CAS  PubMed  Google Scholar 

  5. Tonnesen MG, Feng X, Clark RA. Angiogenesis in wound healing. J Invest Dermatol Symp Proc 2000, 5:40–46

    Article  CAS  Google Scholar 

  6. Takehara K. Growth regulation of skin fibroblasts. J Dermatol Sci 2000; 24:S70–77.

    Article  CAS  PubMed  Google Scholar 

  7. Rockwell WB, Cohen IK, Ehrlich HP. Keloids and hypertrophic scars: A comprehensive review. Plast Reconstr Surg 1989; 84:827–837.

    Article  CAS  PubMed  Google Scholar 

  8. Reed BH, Wilk R, Lipshitz HD. Downregulation of Jun kinase signaling in the amnioserosa is essential for dorsal closure of the Drosophila embryo. Curr Biol 2001; 11:1098–108.

    Article  CAS  PubMed  Google Scholar 

  9. Breuss JM, Gallo J, DeLisser HM et al. Expression of the beta 6 integrin subunit in development, neoplasia and tissue repair suggests a role in epithelial remodeling. J Cell Sci 1995; 108:2241–51.

    CAS  PubMed  Google Scholar 

  10. Haapasalmi K, Zhang K, Tonnesen M et al. Keratinocytes in human wounds express alpha v beta 6 integrin. J Invest Dermatol 1996; 106:42–8.

    Article  CAS  PubMed  Google Scholar 

  11. Liechty KW, Crombleholme TM, Cass DL et al. Diminished interleukin-8 (IL-8) production in the fetal wound healing response. J Surg Res 1998; 77:80–84.

    Article  CAS  PubMed  Google Scholar 

  12. Dang CM, Beanes SR, Soo C et al. Decreased expression of fibroblast and keratinocyte growth factor isoforms and receptors during scarless repair. Plast Reconstr Surg 2003;111:1969–79.

    Article  PubMed  Google Scholar 

  13. Cowin AJ, Brosnan MP, Holmes TM et al. Endogenous inflammatory response to dermal wound healing in the fetal and adult mouse. Dev Dyn 1998; 212:385–93.

    Article  CAS  PubMed  Google Scholar 

  14. Lanning DA, Nwomeh BC, Montante SJ et al. TGF-betal alters the healing of cutaneous fetal excisional wounds. J Pediatr Surg 1999; 34:695–700.

    Article  CAS  PubMed  Google Scholar 

  15. Lin RY, Sullivan KM, Argenta PA et al. Exogenous transforming growth factor-beta amplifies its own expression and induces scar formation in a model of human fetal skin repair. Ann Surg 1995; 222:146–54.

    Article  CAS  PubMed  Google Scholar 

  16. Liechty KW, Adzick NS, Crombleholme TM. Diminished interleukin 6 (IL-6) production during scarless human fetal wound repair. Cytokine 2000; 12:671–6.

    Article  CAS  PubMed  Google Scholar 

  17. Hwang EA, Lee HB, Tark KC. Comparison of bone morphogenetic protein receptors expression in the fetal and adult skin. Yonsei Med J 2001; 42:581–6.

    CAS  PubMed  Google Scholar 

  18. Longaker MT, Chiu ES, Adzick NS et al. Studies in fetal wound healing: V. A prolonged presence of hyaluronic acid characterizes fetal wound fluid. Ann Surg 1991; 213:292–296.

    Article  CAS  PubMed  Google Scholar 

  19. Larjava H, Salo T, Haapasalmi K et al. Expression of integrins and basement membrane components by wound keratinocytes. J Clin Invest 1993; 92:1425–35.

    CAS  PubMed  Google Scholar 

  20. Stepanovic V, Awad O, Jiao C et al. Leprdb diabetic mouse bone marrow cells inhibit skin wound vascularization but promote wound healing. Circ Res 2003; 92:1247–53.

    Article  CAS  PubMed  Google Scholar 

  21. Fagerholm P, Lisha G. Corneal stem cell grafting after chemical injury. Acta Ophthalmol Scand 1999; 77:165–9.

    Article  CAS  PubMed  Google Scholar 

  22. Anderson DF, Ellies P, Pires RT et al. Amniotic membrane transplantation for partial limbal stem cell deficiency. Br J Ophthalmol 2001; 85:567–75.

    Article  CAS  PubMed  Google Scholar 

  23. Moriyama T, Imai E. Role of myofibroblasts in progressive renal diseases. Contrib Nephrol 2003; 139:120–40.

    CAS  PubMed  Google Scholar 

  24. Razzaque MS, Azouz A, Shinagawa T et al. Factors regulating the progression of hypertensive nephrosclerosis. Contrib Nephrol 2003; 139:173–86.

    CAS  PubMed  Google Scholar 

  25. Matsuo S, Morita Y, Maruyama S et al. Proteinuria and tubulointerstitial injury: the causative factors for the progression of renal diseases. Contrib Nephrol 2003; 139:20–31.

    CAS  PubMed  Google Scholar 

  26. Razzaque MS, Taguchi T. Role of glomerular epithelial cell-derived heat shock protein 47 in experimental lipid nephropathy. Kidney Int 1999; 71:S256–9.

    Article  CAS  Google Scholar 

  27. Sund S, Forre O, Berg KJ et al. Morphological and functional renal effects of long-term low-dose cyclosporin A treatment in patients with rheumatoid arthritis. Clin Nephrol 1994; 41:33–40.

    CAS  PubMed  Google Scholar 

  28. Cheng M, Razzaque MS, Nazneen A et al. Expression of the heat shock protein 47 in gentamicin-treated rat kidneys. Int J Exp Pathol 1998; 79:125–32.

    Article  CAS  PubMed  Google Scholar 

  29. Razzaque MS, Hossain MA, Kohno S et al. Bleomycin-induced pulmonary fibrosis in rat is associated with increased expression of collagen-binding heat shock protein (HSP) 47. Virchows Arch 1998; 432:455–60.

    Article  CAS  PubMed  Google Scholar 

  30. Marcellin P, Asselah T, Boyer N. Fibrosis and disease progression in hepatitis C. Hepatology 2002; 36:S47–56.

    Article  PubMed  Google Scholar 

  31. Zorzetto M, Ferrarotti I, Trisolini R et al. Complement receptor 1 gene polymorphisms are associated with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2003; 168:330–4.

    Article  PubMed  Google Scholar 

  32. Chung MP, Monick MM, Hamzeh NY et al. Role of repeated lung injury and genetic background in bleomycin-induced fibrosis. Am J Respir Cell Mol Biol 2003; 29:375–80.

    Article  CAS  PubMed  Google Scholar 

  33. Razzaque MS, Taguchi T. Cellular and molecular events leading to renal tubulointerstitial fibrosis. Med Electron Microsc 2002; 35:68–80.

    Article  CAS  PubMed  Google Scholar 

  34. Razzaque MS, Taguchi T. Pulmonary fibrosis: Cellular and molecular events. Pathol Int 2003; 53:133–45.

    Article  CAS  PubMed  Google Scholar 

  35. Borok Z, Buhl R, Grimes GJ et al. Effect of glutathione aerosol on oxidant-antioxidant imbalance in idiopathic pulmonary fibrosis. Lancet 1991; 338:215–6.

    Article  CAS  PubMed  Google Scholar 

  36. Cantin AM, Fells GA, Hubbard RC et al. Antioxidant macromolecules in the epithelial lining fluid of the normal human lower respiratory tract. J Clin Invest 1990; 86:962–71.

    CAS  PubMed  Google Scholar 

  37. Rohrmoser MM, Mayer G. Reactive oxygen species and glomerular injury. Kidney Blood Press Res 1996; 19:263–9.

    CAS  PubMed  Google Scholar 

  38. Trachtman H, Chan JC, Chan W et al. Vitamin E ameliorates renal injury in an experimental model of immunoglobulin A nephropathy. Pediatr Res 1996; 40:620–6.

    CAS  PubMed  Google Scholar 

  39. Pantelidis P, Southcott AM, Black CM, Du Bois RM. Up-regulation of IL-8 secretion by alveolar macrophages from patients with fibrosing alveolitis: a subpopulation analysis. Clin Exp Immunol 1997; 108:95–104.

    Article  CAS  PubMed  Google Scholar 

  40. Razzaque MS, Foster CS, Ahmed AR. Role of enhanced expression of m-CSF in conjunctiva affected by cicatricial pemphigoid. Invest Ophthalmol Vis Sci 2002; 43:2977–83.

    PubMed  Google Scholar 

  41. Burger-Kentischer A, Goebel H, Seiler R et al. Expression of macrophage migration inhibitory factor in different stages of human atherosclerosis. Circulation 2002; 105:1561–6.

    Article  CAS  PubMed  Google Scholar 

  42. Inan MS, Razzaque MS, Taguchi T. Pathological significance of renal expression of NF-kappa B. Contrib Nephrol 2003;139:90–101.

    Article  CAS  PubMed  Google Scholar 

  43. Burton CJ, Combe C, Walls J et al. Secretion of chemokines and cytokines by human tubular epithelial cells in response to proteins. Nephrol Dial Transplant 1999; 14:2628–33.

    Article  CAS  PubMed  Google Scholar 

  44. Razzaque MS, Ahmed BS, Foster CS et al. Effects of IL-4 on conjunctival fibroblasts: possible role in ocular cicatricial pemphigoid. Invest Ophthalmol Vis Sci 2003; 44:3417–23.

    Article  PubMed  Google Scholar 

  45. Juliano RL, Haskill S. Signal transduction from the extracellular matrix. J Cell Biol 1993; 120:577–85.

    Article  CAS  PubMed  Google Scholar 

  46. Thorne SA, Abbot SE, Stevens CR et al. Modified low density lipoprotein and cytokines mediate monocyte adhesion to smooth muscle cells. Atherosclerosis 1996; 127:167–76.

    Article  CAS  PubMed  Google Scholar 

  47. Senoo H, Hata R. Extracellular matrix regulates and L-ascorbic acid 2-phosphate further modulates morphology, proliferation, and collagen synthesis of perisinusoidal stellate cells. Biochem Biophys Res Commun 1994; 200:999–1006.

    Article  CAS  PubMed  Google Scholar 

  48. Carloni V, Romanelli RG, Pinzani M et al. Expression and function of integrin receptors for collagen and laminin in cultured human hepatic stellate cells. Gastroenterology 1996; 110:1127–36.

    Article  CAS  PubMed  Google Scholar 

  49. Nagata K. Expression and function of heat shock protein 47: a collagen-specific molecular chapter-one in the endoplasmic reticulum. Matrix Biol 1998; 16:379–86.

    Article  CAS  PubMed  Google Scholar 

  50. Razzaque MS, Foster CS, Ahmed AR. Role of collagen-binding heat shock protein 47 and transforming growth factor-beta1 in conjunctival scarring in ocular cicatricial pemphigoid. Invest Ophthalmol Vis Sci 2003; 44:1616–21.

    Article  PubMed  Google Scholar 

  51. Liu D, Razzaque MS, Cheng M et al. The renal expression of heat shock protein 47 and collagens in acute and chronic experimental diabetes in rats. Histochem J 2001; 33:621–8.

    Article  PubMed  Google Scholar 

  52. Razzaque MS, Taguchi T. The possible role of colligin/HSP47, a collagen-binding protein, in the pathogenesis of human and experimental fibrotic diseases. Histol Histopathol 1999; 14:1199–212.

    CAS  PubMed  Google Scholar 

  53. Razzaque MS, Shimokawa I, Nazneen A et al. Life-long dietary restriction modulates the expression of collagens and collagen-binding heat shock protein 47 in aged Fischer 344 rat kidney. Histochem J 1999; 31:123–32.

    Article  CAS  PubMed  Google Scholar 

  54. Razzaque MS, Nazneen A, Taguchi T. Immunolocalization of collagen and collagen-binding heat shock protein 47 in fibrotic lung diseases. Mod Pathol 1998; 11:1183–8.

    CAS  PubMed  Google Scholar 

  55. Razzaque MS, Kumatori A, Harada T et al. Coexpression of collagens and collagen-binding heat shock protein 47 in human diabetic nephropathy and IgA nephropathy. Nephron 1998; 80:434–43.

    Article  CAS  PubMed  Google Scholar 

  56. Zaoui P, Cantin JF, Alimardani-Bessette M et al. Role of metalloproteases and inhibitors in the occurrence and progression of diabetic renal lesions. Diabetes Metab 2000; 4:25–9.

    Google Scholar 

  57. Nagase H, Kashiwagi M. Aggrecanases and cartilage matrix degradation. Arthritis Res Ther 2003; 5:94–103.

    Article  CAS  PubMed  Google Scholar 

  58. Yaguchi T, Fukuda Y, Ishizaki M et al. Immunohistochemical and gelatin zymography studies for matrix metalloproteinases in bleomycin-induced pulmonary fibrosis. Pathol Int 1998; 48:954–63.

    Article  CAS  PubMed  Google Scholar 

  59. Madtes DK, Elston AL, Kaback LA et al. Selective induction of tissue inhibitor of metalloproteinase-1 in bleomycin-induce pulmonary fibrosis. Am J Respir Cell Mol Biol 2001; 24:599–607.

    CAS  PubMed  Google Scholar 

  60. Jiang Z, Seo JY, Ha H et al. Reactive oxygen species mediate TGF-beta1-induced plasminogen activator inhibitor-1 upregulation in mesangial cells. Biochem Biophys Res Commun. 2003; 309:961–966.

    Article  CAS  PubMed  Google Scholar 

  61. Rechardt O, Elomaa O, Vaalamo M et al. Stromelysin-2 is upregulated during normal wound repair and is induced by cytokines. J Invest Dermatol 2000; 115:778–787

    Article  CAS  PubMed  Google Scholar 

  62. Mast BA, Diegelmann RF, Krummel TM et al. Scarless wound healing in the mammalian fetus. Surg Gynecol Obstet 1992; 174:441–51.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Oral and Developmental Biology, Harvard School of Dental Medicine, The Forsyth Institute, Boston, Massachusetts, USA

    Mohammed S. Razzaque M.D., Ph.D.

  2. Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA

    Moussa El-Hallak & Abdallah Azouz

  3. Department of Pathology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan

    Takashi Taguchi

Authors
  1. Mohammed S. Razzaque M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Moussa El-Hallak
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Abdallah Azouz
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Takashi Taguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

Copyright information

© 2005 Eurekah.com and Kluwer Academic / Plenum Publishers

About this chapter

Cite this chapter

Razzaque, M.S., El-Hallak, M., Azouz, A., Taguchi, T. (2005). Tissue Scarring. In: Fibrogenesis: Cellular and Molecular Basis. Medical Intelligence Unit. Springer, Boston, MA. https://doi.org/10.1007/0-387-26476-0_1

Download citation

Publish with us

Policies and ethics

Search

Navigation