Proteases and Protease Inhibitors in Tissue Repair

  • Chapter
Peritoneal Surgery

Abstract

Healing of wounds in the peritoneum and the skin may seem to be quite different, but at the molecular level they share many common aspects. For example, both peritoneal and skin wound healing involve inflammation, chemotactic migration, mitosis and differentiation of wound cells, and synthesis or remodeling of extracellular matrix. In this chapter, we describe the roles of matrix metalloproteinases and their tissue inhibitors in normal and abnormal wound healing in the skin.

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

Access this chapter

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free ship** worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free ship** 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.

Similar content being viewed by others

References

  1. Woessner JF Jr. The matrix metalloproteinase family. In: Parks WC, Mecham RP, eds. Matrix Metalloproteinases. San Diego: Academic Press, 1998:1–14.

    Chapter  Google Scholar 

  2. Parks WC, Mecham RP. Matrix metalloproteinases. In: Mecham RP, ed. Biology of the Extracellular Matrix. San Diego. Academic Press, 1998:1–362.

    Google Scholar 

  3. Shapiro SD. Matrix metalloproteinase degradation of extracellular matrix: biological consequences. Curr Opin Cell Biol 1998; 10:602–608.

    Article  PubMed  CAS  Google Scholar 

  4. Jeffrey JJ. Interstitial collagenases. In: Parks WC, Mecham RP, eds. Matrix Metalloproteinases. San Diego: Academic Press, 1998:15–42.

    Chapter  Google Scholar 

  5. Welgus HG, Jeffrey JJ, Eisen AZ. The collagen substrate specificity of human skin fibroblast collagenase. J Biol Chem 1981; 256:9511–9515.

    PubMed  CAS  Google Scholar 

  6. Saarialho-Kere UK, Chang ES, Welgus HG, Parks WC. Distinct localization of collagenase and TIMP expression in wound healing associated with ulcerative pyogenic granu-loma.J Clin Invest 1992: 90:1952–1957.

    Article  PubMed  CAS  Google Scholar 

  7. Saarialho-Kere UK, Kovacs SO, Petland AP, Olerud J, Welgus HG, Parks WC. Cell-matrix interactions modulate interstitial collagenase expression by keratinocytes actively involved in wound healing. J Clin Invest 1993; 92:2858–2866.

    Article  PubMed  CAS  Google Scholar 

  8. Stricklin GP, Li L, Jancic V, Wenczak BA, Nanney LB. Localization of mRNAs representing collagenase and TIMP in sections of healing human burn wounds. Am J Pathol 1993: 143:1657–1666.

    PubMed  CAS  Google Scholar 

  9. Wolfe GC, MacNaul KL, Beuchel FF, et al. Differential in vivo expression of collagenase messenger RNA in syn-ovium and cartilage. Arthritis Rheum 1993; 36:1540–1557.

    Article  PubMed  CAS  Google Scholar 

  10. Fisher C, Gilbertson-Beadling S, Powers EA, Petzold G, Poorman R, Mitchell MA. Interstitial collagenase is required for angiogenesis in vitro. Dev Biol 1994; 162:499–510.

    Article  PubMed  CAS  Google Scholar 

  11. Galis ZS, Sukhova GK, Lark MW, Libby P. Increased expression of matrix metalloproteinases and matrix degrading activity in vulnerable regions of human atherosclerotic plaques.J Clin Invest 1994; 94:2493–2503.

    Article  PubMed  CAS  Google Scholar 

  12. Hasty KA, Pourmotabbed TF, Goldberg GI, et al. Human neutrophil collagenase. A distinct gene product with ho-mology to other matrix metalloproteinases. J Biol Chem 1990: 265:11421–11424.

    PubMed  CAS  Google Scholar 

  13. Chubinskaya S, Huch K, Mikecz K, et al. Chordrocyte matrix metalloproteinase-8: up-regulation of neutrophil collagenase by interleukin-1 beta in human cartilage from knee and ankle joints. Lab Invest 1996; 74:232–240.

    PubMed  CAS  Google Scholar 

  14. Freije JM, Diez-Itza I, Balbin M, et al. Molecular cloning and expression of collagenase-3, a novel human matrix metalloproteinase produced by breast carcinomas. J Biol Chem 1994: 269:16766–16773.

    PubMed  CAS  Google Scholar 

  15. Mitchell PG, Magna HA, Reeves LM, et al. Cloning, expression, and type II collagenolytic activity of matrix met-alloproteinase-13 from human osteoarthritic cartilage. J Clin Invest 1996; 97:761–768.

    Article  PubMed  CAS  Google Scholar 

  16. Reboul P, Pelletier JP, Tardif G, Gloutier JM, Martel-Pelletier J. The new collagenase, collagenase-3, is expressed and synthesized by human chondrocytes but not by syn-oviocytes. A role in osteoarthritis. J Clin Invest 1996; 97:2011–2019.

    Article  PubMed  CAS  Google Scholar 

  17. Gack S, Vallon R, Schmidt J, et al. Expression of interstitial collagenase during skeletal development of the mouse is restricted to osteoblast-like cells and hypertrophie chondrocytes. Cell Growth Differ 1994; 6:759–767.

    Google Scholar 

  18. Knauper V, Murphy G. Collagenase-3 (MMP-13) is expressed by hypertrophic chondrocytes, periosteal cells, and osteoblast during human fetal bone development. Dev Dyn 1997; 208:387–397.

    Article  Google Scholar 

  19. Vu TH, Werb Z. Gelatinase B: structure, regulation, and function. In: Parks WC, Mecham RP, eds. Matrix Metallo-proteinases. San Diego: Academic Press, 1998:115–149.

    Chapter  Google Scholar 

  20. Yu AE, Murphey AN, Stetler-Stevenson WG. 72-kDa gelati-nase (gelatinase A): structure, activation, regulation and substrate specificity. In: Parks WC, Mecham RP, eds. Matrix Metalloproteinases. San Diego: Academic Press, 1998: 85–114.

    Chapter  Google Scholar 

  21. Overall CM, Sodek J. Concanavalin A produces a matrix-degradative phenotype in human fibroblasts. Induction and endogenous activation of collagenase, 72-kDa gelatinase, and PUMP-1 is accompanied by the suppression of the tissue inhibitor of matrix metalloproteinases. J Biol Chem 1990; 256:21141–21151.

    Google Scholar 

  22. Stahle-Backdahl M, Parks WC. 92-kDa gelatinase is actively expressed by eosinophils and secreted by neutrophils in invasive squamous cell carcinoma. Am J Pathol 1993; 142:995–1000.

    PubMed  CAS  Google Scholar 

  23. Stahle-Backdahl M, Inoue M, Giudice GJ, Parks WC. 92-kDa gelatinase is produced by eosinophils at the site of blister formation in bullous pemphigoid and cleaves the extracellular domain of the 180-kDa bullous pemphigoid autoantigen. J Clin Invest 1994; 93:2202–2230.

    Article  Google Scholar 

  24. Fini ME, Cook JR, Mohan R, Brinckerhoff CE. Regulation of matrix metalloproteinase gene expression. In: Parks WC, Mecham RP, eds. Matrix Metalloproteinases. San Diego: Academic Press, 1998:300–356.

    Google Scholar 

  25. Murphy G, Cockett MI, Ward RV, Docherty AJP. Matrix metalloproteinase degradation of elastin, type IV collagen and proteoglycan. A quantitative comparison of the activities of 95-kDa and 75-kDa gelatinases stromelysins-1 and-2 and punctuated metalloproteinase (PUMP). Biochem J 1991; 277:277–279.

    PubMed  CAS  Google Scholar 

  26. Nagase H. Stromelysins 1 and 2. In: Parks WC, Mecham RP, eds. Matrix Metalloproteinases. San Diego: Academic Press, 1998:43–84.

    Chapter  Google Scholar 

  27. Pei D, Weiss SJ. Furin-dependent intracellular activation of the human stromelysin-3 zymogen. Nature (Lond) 1995; 375:244–247.

    Article  CAS  Google Scholar 

  28. Knauper V, Murphy G. Membrane-type matrix metalloproteinases and cell surface-associated activation cascades for matrix metalloproteinases. In: Parks WC, Mecham RP, eds. Matrix Metalloproteinases. San Diego: Academic Press, 1998:199–218.

    Chapter  Google Scholar 

  29. Wilson CL, Matrisian LM. Matrilysin. In: Parks WC, Mecham RP, eds. Matrix Metalloproteinases. San Diego: Academic Press, 1998:149–184.

    Chapter  Google Scholar 

  30. Halpert I, Roby JD, Sires UI, et al. Matrilysin is expressed by lipid-laden macrophages at sites of potential rupture in atherosclerotic lesions and localizes to areas of versican deposition, a proteoglycan substrate for the enzyme. Proc Natl Acad Sci USA 1996; 93:9748–9753.

    Article  PubMed  CAS  Google Scholar 

  31. Sires UI, Griffin GL, Broekelmann T, et al. Degradation of entactin by matrix metalloproteinases. Susceptibility to matrilysin and identification of cleavage sites. J Biol Chem 1993; 268:2069–2074.

    PubMed  CAS  Google Scholar 

  32. Shapiro SD. Macrophage elastase (MMP-12). In: Parks WC, Mecham RP, eds. Matrix Metalloproteinases. San Diego: Academic Press, 1998:185–198.

    Chapter  Google Scholar 

  33. Hayakawa T, Yamashita K, Uchujima E, Iwata K. Growth promoting activity of tissue inhibitor of metalloproteinase-1 (TIMP-1) for a wide range of cells. FEBS Lett 1992; 298:29–32.

    Article  PubMed  CAS  Google Scholar 

  34. Goldberg GI, Wilhelm SM, Kronberger A, Bauer EA, Grant GA, Eisen AZ. Human fibroblast collagenase. Complete primary structure and homology to an oncogene transformation-induced rat protein. J Biol Chem 1986; 261:6600–6605.

    PubMed  CAS  Google Scholar 

  35. Murphy G, Allan JA, Willenbrock F, Cockett MI, O’Con-nell JP, Docherty AJP. The C-terminal domain in collagenase and stromelysin specificity. J Biol Chem 1992; 267:9612–9618.

    PubMed  CAS  Google Scholar 

  36. Van Wart HE, Birkedal-Hansen H. The cysteine switch: a principle of regulation of metalloproteinase activity with potential applicability to the entire matrix metalloproteinase gene family. Proc Natl Acad Sci USA 1990; 87:5578–5582.

    Article  PubMed  Google Scholar 

  37. Murphy G, Willenbrock F, Ward RV, Cockett MI, Eaton D, Docherty AJP. The C-terminal domain of 72-kDa gelatinase A is not required for catalysis, but is essential for membrane activation and modulates interactions with tissue inhibitors of metalloproteinases. Biochem J 1992; 283:637–641.

    PubMed  CAS  Google Scholar 

  38. O’Connell JP, Willenbrock F, Docherty AJP, Eaton D, Murphy G. Analysis of the role of the COOH-terminal domain in the activation, proteolytic activity, and tissue inhibitor of metalloproteinase interactions of gelatinase B. J Biol Chem 1994; 269:14967–14973.

    PubMed  Google Scholar 

  39. Baragi VM, Fliszar CJ, Conroy MC, Ye QZ, Shipley JM, Wel-gus HG. Contribution of the C-terminal domain of metalloproteinases to binding by tissue inhibitor of metalloproteinases. C-terminal truncated stromelysin and matrilysin exhibit equally compromised binding affinities as compared to full-length stromelysin. J Biol Chem 1994; 269:12692–12697.

    PubMed  CAS  Google Scholar 

  40. Murphy G, Nguyen Q, Cockett ML, et al. Assessment of the role of the fibronectin-like domain of gelatinase A by analysis of a deletion mutant. J Biol Chem 1994; 269:6632–6636.

    PubMed  CAS  Google Scholar 

  41. Pilcher BK, Dumin JA, Sudbeck BD, Krane SM, Welgus HG, Parks WC. The activity of collagenase-1 is required for keratinocyte migration on a type I collagen matrix. J Cell Biol 1997; 137:1445–1457.

    Article  PubMed  CAS  Google Scholar 

  42. Saarialho-Kere UK, Vaalamo M, Karjalainen-Lindsberg ML, Airola K, Parks WC, Puolakkainen P. Enhanced expression of matrilysin, collagenase, and stromelysin-1 in gastrointestinal ulcers. Am J Pathol 1996; 148:519–526.

    PubMed  CAS  Google Scholar 

  43. Dunsmore SE, Saarialho-Kere UK, Roby JD, et al. Matrilysin function and expression in airway epithelium. J Clin Invest 1998; 102:1321–1331.

    Article  PubMed  CAS  Google Scholar 

  44. Sudbeck BD, Pilcher BK, Welgus HG, Parks WC. Induction and repression of collagenase-1 by keratinocytes is controlled by distinct components of different extracellular matrix compartments.J Biol Chem 1997; 272:22103–22110.

    Article  PubMed  CAS  Google Scholar 

  45. Mauviel A, Uitto J. The extracellular matrix in wound healing: role of the cytokine network. Wounds 1993; 5:137–152.

    Google Scholar 

  46. Bucalo B, Eaglstein WH, Falanga V. Inhibition of cell proliferation by chronic wound fluid. Wound Repair Regen 1993; 1:181–186.

    Article  PubMed  CAS  Google Scholar 

  47. Katz MH, Alvarez AF, Kirsner RS, Eaglstein WH, Falanga V. Human wound fluid from acute wounds stimulates fibro-blast and endothelial cell growth. J Am Acad Dermatol 1991; 25:1054–1058.

    Article  PubMed  CAS  Google Scholar 

  48. Harris IR, Yee KC, Walters CE, et al. Cytokine and protease levels in healing and non-healing chronic venous leg ulcers. Exp Dermatol 1995; 4:342–349.

    Article  PubMed  CAS  Google Scholar 

  49. Yager DR, Zhang L, Liang H, Diegelmann RF, Cohen IK. Wound fluids from human pressure ulcers contain elevated matrix metalloproteinase levels and activity compared to surgical wound fluid. J Invest Dermatol 1996; 107:743–748.

    Article  PubMed  CAS  Google Scholar 

  50. Rogers AA, Burnett S, Moore JC, Shakespeare PG, Chen WYJ. Involvement of proteolytic enzymes, plasminogen activators and matrix metalloproteinases in the pathophysi-ology of pressure ulcers. Wound Repair Regen 1995; 3:273–283.

    Article  PubMed  CAS  Google Scholar 

  51. Bullen EC, Longaker MT, Updike DL, Benton R, Ladin D, Hou Z. Tissue inhibitor of metalloproteinases-1 is decreased and activated gelatinases are increased in chronic wounds. J Invest Dermatol 1995; 104:236–240.

    Article  PubMed  CAS  Google Scholar 

  52. Rao CN, Ladin DA, Liu YY, Chilukuri K, Hou ZZ, Woodley DT. αl-Antitrypsin is degraded and non-functional in chronic wounds but intact and functional in acute wounds: the inhibitor protects fibronectin from degradation by chronic wound fluid enzymes. J Invest Dermatol 1995; 105:572–578.

    Article  PubMed  CAS  Google Scholar 

  53. Wysocki AB, Staiano-Coico L, Grinnell F. Wound fluid from chronic leg ulcers contains elevated levels of metalloproteinases MMP-2 and MMP-9. J Invest Dermatol 1993; 101:64–68.

    Article  PubMed  CAS  Google Scholar 

  54. Grinnell F, Zhu M. Fibronectin degradation in chronic wounds depends on the relative levels of elastase, 1-pro-teinase inhibitor, and α2-macroglobulin. J Invest Dermatol 1996; 106:335–341.

    Article  PubMed  CAS  Google Scholar 

  55. Yager DR, Chen SM, Ward SI, Olutoye OO, Diegelmann RF, Cohen IK. Ability of chronic wound fluids to degrade peptide growth factors is associated with increased levels of elastase activity and diminished levels of proteinase inhibitors. Wound Repair Regen 1997; 5:23–32.

    Article  Google Scholar 

  56. Wlaschek M, Pees D, Achterberg V, Meyer-Ingold W, Scharfetter-Kochanek K. Protease inhibitors protect growth factor activity in chronic wounds. Br J Dermatol 1997; 137:646–647.

    Article  PubMed  CAS  Google Scholar 

  57. Bennett NT, Schultz GS. Growth factors and wound healing: Part II. Role in normal and chronic wound healing. Am J Surg 1993; 166:74–81.

    Article  PubMed  CAS  Google Scholar 

  58. Cooper DM, Yu EZ, Hennessey P, Ko F, Robson MC. Determination of endogenous cytokines in chronic wounds. Ann Surg 1994; 219:688–692.

    Article  PubMed  CAS  Google Scholar 

  59. Steed DL, Donohoe D, Webster MW, Lindsley L. Effect of extensive debridement and treatment on the healing of diabetic foot ulcers. J Am Coll Surg 1996; 183:61–64.

    PubMed  CAS  Google Scholar 

Download references

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2000 Springer Science+Business Media New York

About this chapter

Cite this chapter

Parks, W.C., Schultz, G.S. (2000). Proteases and Protease Inhibitors in Tissue Repair. In: diZerega, G.S. (eds) Peritoneal Surgery. Springer, New York, NY. https://doi.org/10.1007/978-1-4612-1194-5_7

Download citation

  • DOI: https://doi.org/10.1007/978-1-4612-1194-5_7

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4612-7040-9

  • Online ISBN: 978-1-4612-1194-5

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Navigation