PDF herunterladen
Thromb Haemost 2003; 90(06): 986-992
DOI: 10.1160/TH03-06-0399
Theme Issue Article
Schattauer GmbH

Matricellular proteins as modulators of wound healing and the foreign body response

Themis R. Kyriakides
1   Departments of Biochemistry, University of Washington, Seattle, Washington, USA
,
Paul Bornstein
1   Departments of Biochemistry, University of Washington, Seattle, Washington, USA
2   Departments of Medicine, University of Washington, Seattle, Washington, USA
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Received 25. Juni 2003

Accepted after resubmission 24. September 2003

Publikationsdatum:
05. Dezember 2017 (online)

Auch verfügbar auf
    Lizenzen und Reprints

Summary

Matricellular proteins form a group of extracellular matrix (ECM) proteins that do not subserve a primary structural role, but rather function as modulators of cell-matrix interactions (1). Members of the group, including thrombospondin (TSP) -1, TSP-2, SPARC, tenascin (TN)-C, and osteopontin (OPN), have been shown to participate in a number of processes related to tissue repair. Specifically, studies in knockout mice have indicated that a deficiency in one or more of these proteins can alter the course of wound healing. More recently, TSP1, TSP2, and SPARC have also been implicated in the foreign body response, an unusual reaction to injury that occurs after the implantation of biomaterials. This review will focus on the roles of these proteins in the response to injury in mice and will show how studies of this pathophysiological process can elucidate some of the intrinsic properties of these matricellular proteins.

Keywords

Matricellular proteins - wound healing - foreign body response - thrombospondin - cell-matrix interactions
 

  • References

  • 1 Bornstein P, Sage EH. Matricellular proteins: extracellular modulators of cell function. Curr Opin Cell Biol 2002; 14: 608-16.
    CrossrefPubMedGoogle Scholar
  • 2 Adams JC, Watt FM. Regulation of development and differentiation by the extracellular matrix. Development 1993; 117: 1183-98.
    PubMedGoogle Scholar
  • 3 Aumailley M, Gayraud B. Structure and biological activity of the extracellular matrix. J Mol Med 1998; 76: 253-65.
    CrossrefPubMedGoogle Scholar
  • 4 Slater M. Dynamic interactions of the extracellular matrix. Histol Histopathol 1996; 11: 175-80.
    PubMedGoogle Scholar
  • 5 Lawler J. The functions of thrombospondin-1 and-2. Curr Opin Cell Biol 2000; 12: 634-40.
    CrossrefPubMedGoogle Scholar
  • 6 Adams JC. Thrombospondins: multifunctional regulators of cell interactions. Annu Rev Cell Dev Biol 2001; 17: 25-51.
    CrossrefPubMedGoogle Scholar
  • 7 Murphy-Ullrich JE. The de-adhesive activity of matricellular proteins: is intermediate cell adhesion an adaptive state?. J Clin Invest 2001; 107: 785-790.
    CrossrefPubMedGoogle Scholar
  • 8 Chen H, Herndon ME, Lawler J. The cell biology of thrombospondin-1. Matrix Biol 2000; 19: 597-614.
    CrossrefPubMedGoogle Scholar
  • 9 Bornstein P, Armstrong LC, Hankenson KD. et al. Thrombospondin 2, a matricellular protein with diverse functions. Matrix Biol 2000; 19: 557-68.
    CrossrefPubMedGoogle Scholar
  • 10 Brekken RA, Sage EH. SPARC, a matricellular protein: at the crossroads of cell-matrix. Matrix Biol 2000; 19: 569-80.
    CrossrefPubMedGoogle Scholar
  • 11 Giachelli CM, Steitz S. Osteopontin: a versatile regulator of inflammation and biomineralization. Matrix Biol 2000; 19: 615-22.
    CrossrefPubMedGoogle Scholar
  • 12 Jones PL, Jones FS. Tenascin-C in development and disease: gene regulation and cell function. Matrix Biol 2000; 19: 581-96.
    CrossrefPubMedGoogle Scholar
  • 13 Mo FE, Muntean AG, Chen CC. et al. CYR61 (CCN1) is essential for placental development and vascular integrity. Mol Cell Biol 2002; 22: 8709-20.
    CrossrefPubMedGoogle Scholar
  • 14 Ivkovic S, Yoon BS, Popoff SN. et al. Connective tissue growth factor coordinates chondrogenesis and angiogenesis during skeletal development. Development 2003; 130: 2779-91.
    CrossrefPubMedGoogle Scholar
  • 15 Latinkic BV, Mo FE, Greenspan JA. et al. Promoter function of the angiogenic inducer Cyr61gene in transgenic mice: tissue specificity, inducibility during wound healing, and role of the serum response element. Endocrinology 2001; 142: 2549-57.
    CrossrefPubMedGoogle Scholar
  • 16 Igarashi A, Okochi H, Bradham DM. et al. Regulation of connective tissue growth factor gene expression in human skin fibroblasts and during wound repair. Mol Biol Cell 1993; 4: 637-45.
    CrossrefPubMedGoogle Scholar
  • 17 Chen CC, Mo FE, Lau LF. The angiogenic factor Cyr61 activates a genetic program for wound healing in human skin fibroblasts. J Biol Chem 2001; 276: 47329-37.
    CrossrefPubMedGoogle Scholar
  • 18 Singer AJ, Clark RA. Cutaneous wound healing. N Engl J Med 1999; 341: 738-46.
    CrossrefPubMedGoogle Scholar
  • 19 Clark RAF. editor. Wound repair: Overview and general considerations. New York: Plenum Press; 1996: 3-50.
    Google Scholar
  • 20 Desmouliere A, Redard M, Darby I. et al. Apoptosis mediates the decrease in cellularity during the transition between granulation tissue and scar. Am J Pathol 1995; 146: 56-66.
    PubMedGoogle Scholar
  • 21 Anderson JM. Inflammatory response to implants. ASAIO Trans 1988; 34: 101-7.
    CrossrefPubMedGoogle Scholar
  • 22 Mikos AG, McIntire LV, Anderson JM. et al. Host response to tissue engineered devices. Adv Drug Deliv Rev 1998; 33: 111-39.
    CrossrefPubMedGoogle Scholar
  • 23 Anderson JM. Multinucleated giant cells. Curr Opin Hematol 2000; 7: 40-7.
    CrossrefPubMedGoogle Scholar
  • 24 Kyriakides TR, Tam JW, Bornstein P. Accelerated wound healing in mice with a disruption of the thrombospondin 2 gene. J Invest Dermatol 1999; 113: 782-7.
    CrossrefPubMedGoogle Scholar
  • 25 Kyriakides TR, Zhu YH, Yang Z. et al. Altered extracellular matrix remodeling and angiogenesis in sponge granulomas of thrombospondin 2-null mice. Am J Pathol 2001; 159: 1255-62.
    CrossrefPubMedGoogle Scholar
  • 26 Kyriakides TR, Leach KJ, Hoffman AS. et al. Mice that lack the angiogenesis inhibitor, thrombospondin 2, mount an altered foreign body reaction characterized by increased vascularity. Proc Natl Acad Sci U S A 1999; 96: 4449-54.
    CrossrefPubMedGoogle Scholar
  • 27 Woodward SC. How fibroblasts and giant cells encapsulate implants: considerations in design of glucose sensors. Diabetes Care 1982; 5: 278-81.
    CrossrefPubMedGoogle Scholar
  • 28 Sharkawy AA, Klitzman B, Truskey GA. et al. Engineering the tissue which encapsulates subcutaneous implants. I. Diffusion properties. J Biomed Mater Res 1997; 37: 401-12.
    CrossrefPubMedGoogle Scholar
  • 29 Vistnes LM, Ksander GA, Kosek J. Study of encapsulation of silicone rubber implants in animals. A foreign-body reaction. Plast Reconstr Surg 1978; 62: 580-8.
    CrossrefPubMedGoogle Scholar
  • 30 Davidson JM, Klagsbrun M, Hill KE. et al. Accelerated wound repair, cell proliferation, and collagen accumulation are produced by a cartilage-derived growth factor. J Cell Biol 1985; 100: 1219-27.
    CrossrefPubMedGoogle Scholar
  • 31 Fajardo LF, Kowalski J, Kwan HH. et al. The disc angiogenesis system. Lab Invest 1988; 58: 718-24.
    PubMedGoogle Scholar
  • 32 Bradshaw AD, Reed MJ, Carbon JG. et al. Increased fibrovascular invasion of subcutaneous polyvinyl alcohol sponges in SPARC-null mice. Wound Repair Regen 2001; 9: 522-30.
    CrossrefPubMedGoogle Scholar
  • 33 Bornstein P. Thrombospondins as matricellular modulators of cell function. J Clin Invest 2001; 107: 929-34.
    CrossrefPubMedGoogle Scholar
  • 34 Murphy-Ullrich JE, Poczatek M. Activation of latent TGF-beta by thrombospondin-1: mechanisms and physiology. Cytokine Growth Factor Rev 2000; 11: 59-69.
    CrossrefPubMedGoogle Scholar
  • 35 Kyriakides TR, Zhu YH, Smith LT. et al. Mice that lack thrombospondin 2 display connective tissue abnormalities that are associated with disordered collagen fibrillogenesis, an increased vascular density, and a bleeding diathesis. J Cell Biol 1998; 140: 419-30.
    CrossrefPubMedGoogle Scholar
  • 36 Kyriakides TR, Rojnuckarin P, Reidy MA. et al. Megakaryocytes require thrombospondin-2 for normal platelet formation and function. Blood 2003; 101: 3915-23.
    CrossrefPubMedGoogle Scholar
  • 37 Kyriakides TR, Zhu YH, Yang Z. et al. The distribution of the matricellular protein thrombospondin 2 in tissues of embryonic and adult mice. J Histochem Cytochem 1998; 46: 1007-15.
    CrossrefPubMedGoogle Scholar
  • 38 Bornstein P, Kyriakides TR, Yang Z. et al. Thrombospondin 2 modulates collagen fibril-logenesis and angiogenesis. J Investig Dermatol Symp Proc 2000; 5: 61-6.
    CrossrefPubMedGoogle Scholar
  • 39 Agah A, Kyriakides TR, Lawler J, Bornstein P. The lack of thrombospondin-1 (TSP1) dictates the course of wound healing in double-TSP1/TSP2-null mice. Am J Pathol 2002; 161: 831-9.
    CrossrefPubMedGoogle Scholar
  • 40 Raugi GJ, Olerud JE, Gown AM. Thrombospondin in early human wound tissue. J Invest Dermatol 1987; 89: 551-4.
    CrossrefPubMedGoogle Scholar
  • 41 DiPietro LA, Nissen NN, Gamelli RL. et al. Thrombospondin 1 synthesis and function in wound repair. Am J Pathol 1996; 148: 1851-60.
    PubMedGoogle Scholar
  • 42 Streit M, Velasco P, Riccardi L. et al. Thrombospondin-1 suppresses wound healing and granulation tissue formation in the skin of transgenic mice. Embo J 2000; 19: 3272-82.
    CrossrefPubMedGoogle Scholar
  • 43 Bradshaw AD, Sage EH. SPARC, a matricellular protein that functions in cellular differentiation and tissue response to injury. J Clin Invest 2001; 107: 1049-54.
    CrossrefPubMedGoogle Scholar
  • 44 Gilmour DT, Lyon GJ, Carlton MB. et al. Mice deficient for the secreted glycoprotein SPARC/osteonectin/BM40 develop normally but show severe age-onset cataract formation and disruption of the lens. Embo J 1998; 17: 1860-70.
    CrossrefPubMedGoogle Scholar
  • 45 Bassuk JA, Birkebak T, Rothmier JD. et al. Disruption of the Sparc locus in mice alters the differentiation of lenticular epithelial cells and leads to cataract formation. Exp Eye Res 1999; 68: 321-31.
    CrossrefPubMedGoogle Scholar
  • 46 Delany AM, Amling M, Priemel M. et al. Osteopenia and decreased bone formation in osteonectin-deficient mice. J Clin Invest 2000; 105: 1325
    CrossrefPubMedGoogle Scholar
  • 47 Bradshaw AD, Reed MJ, Sage EH. SPARC-null mice exhibit accelerated cutaneous wound closure. J Histochem Cytochem 2002; 50: 1-10.
    CrossrefPubMedGoogle Scholar
  • 48 Basu A, Kligman LH, Samulewicz SJ. et al. Impaired wound healing in mice deficient in a matricellular protein SPARC (osteonectin, BM-40). BMC Cell Biol 2001; 2: 15
    CrossrefPubMedGoogle Scholar
  • 49 Liaw L, Birk DE, Ballas CB. et al. Altered wound healing in mice lacking a functional osteopontin gene (spp1). J Clin Invest 1998; 101: 1468-78.
    CrossrefPubMedGoogle Scholar
  • 50 Forsberg E, Hirsch E, Frohlich L. et al. Skin wounds and severed nerves heal normally in mice lacking tenascin-C. Proc Natl Acad Sci USA 1996; 93: 6594-9.
    CrossrefPubMedGoogle Scholar
  • 51 Mackie EJ, Halfter W, Liverani D. Induction of tenascin in healing wounds. J Cell Biol 1988; 107: 2757-67.
    CrossrefPubMedGoogle Scholar
  • 52 Midwood KS, Schwarzbauer JE. Tenascin-C modulates matrix contraction via focal adhesion kinase- and Rho-mediated signaling pathways. Mol Biol Cell 2002; 13: 3601-13.
    CrossrefPubMedGoogle Scholar
  • 53 Mao JR, Taylor G, Dean WB. et al. Tenascin-X deficiency mimics Ehlers-Danlos syndrome in mice through alteration of collagen deposition. Nat Genet 2002; 30: 421-5.
    CrossrefPubMedGoogle Scholar
  • 54 Yang Z, Kyriakides TR, Bornstein P. Matricellular proteins as modulators of cell-matrix interactions: adhesive defect in thrombospondin 2-null fibroblasts is a consequence of increased levels of matrix metalloproteinase-2. Mol Biol Cell 2000; 11: 3353-64.
    CrossrefPubMedGoogle Scholar
  • 55 Schultz-Cherry S CH, Mosher DF, Misenheimer TM. et al. Regulation of transforming growth factor-beta activation by discrete sequences of thrombospondin 1. J Biol Chem 1995; 270: 7304-10.
    CrossrefPubMedGoogle Scholar
  • 56 Kyriakides TR, Hartzel T, Huynh G. et al. Regulation of angiogenesis and matrix remodeling by localized, matrix- mediated antisense gene delivery. Mol Ther 2001; 3: 842-9.
    CrossrefPubMedGoogle Scholar
  • 57 Kyriakides TR, Cheung CY, Murthy N. et al. pH-sensitive polymers that enhance intracellular drug delivery in vivo. J Control Release 2002; 78: 295-303.
    CrossrefPubMedGoogle Scholar
  • 58 Puolakkainen P, Bradshaw AD, Kyriakides TR. et al. Compromised production of extracellular matrix in mice lacking secreted protein, acidic and rich in cysteine (SPARC) leads to a reduced foreign body reaction to implanted biomaterials. Am J Pathol 2003; 162: 627-35.
    CrossrefPubMedGoogle Scholar
  • 59 Steitz SA, Speer MY, McKee MD. et al. Osteopontin inhibits mineral deposition and promotes regression of ectopic calcification. Am J Pathol 2002; 161: 2035-46.
    CrossrefPubMedGoogle Scholar
  • 60 Speer MY, McKee MD, Guldberg RE. et al. Inactivation of the osteopontin gene enhances vascular calcification of matrix Gla protein-deficient mice: evidence for osteopontin as an inducible inhibitor of vascular calcification in vivo. J Exp Med 2002; 196: 1047-55.
    CrossrefPubMedGoogle Scholar
  • 61 Weber GF, Zawaideh S, Hikita S. et al. Phosphorylation-dependent interaction of osteopontin with its receptors regulates macrophage migration and activation. J Leukoc Biol 2002; 72: 752-61.
    PubMedGoogle Scholar
  • 62 Singh RP, Patarca R, Schwartz J. et al. Definition of a specific interaction between the early T lymphocyte activation 1 (Eta-1) protein and murine macrophages in vitro and its effect upon macrophages in vivo. J Exp Med 1990; 171: 1931-42.
    CrossrefPubMedGoogle Scholar
  • 63 Ratner BD. Reducing capsular thickness and enhancing angiogenesis around implant drug release systems. J Control Release 2002; 78: 211-8.
    CrossrefPubMedGoogle Scholar