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

2003 ◽  
Vol 90 (12) ◽  
pp. 986-992 ◽  
Author(s):  
Themis Kyriakides ◽  
Paul Bornstein
Keyword(s):  
Wound Healing ◽  
Foreign Body ◽  
Tissue Repair ◽  
Foreign Body Response ◽  
Matricellular Proteins ◽  
Cell Matrix ◽  
Ecm Proteins ◽  
Matrix Interactions ◽  
Cell Matrix Interactions ◽  
Body Response

SummaryMatricellular 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.

Substrates of Factor XIII-A: roles in thrombosis and wound healing

2012 ◽  
Vol 124 (3) ◽  
pp. 123-137 ◽  
Author(s):  
Victoria R. Richardson ◽  
Paul Cordell ◽  
Kristina F. Standeven ◽  
Angela M. Carter
Keyword(s):  
Wound Healing ◽  
Factor Xiii ◽  
Tissue Repair ◽  
Cross Linking ◽  
Clot Retraction ◽  
Matrix Deposition ◽  
Cell Matrix ◽  
Matrix Interactions ◽  
Cell Matrix Interactions

FXIII (Factor XIII) is a Ca2+-dependent enzyme which forms covalent ϵ-(γ-glutamyl)lysine cross-links between the γ-carboxy-amine group of a glutamine residue and the ϵ-amino group of a lysine residue. FXIII was originally identified as a protein involved in fibrin clot stabilization; however, additional extracellular and intracellular roles for FXIII have been identified which influence thrombus resolution and tissue repair. The present review discusses the substrates of FXIIIa (activated FXIII) involved in thrombosis and wound healing with a particular focus on: (i) the influence of plasma FXIIIa on the formation of stable fibrin clots able to withstand mechanical and enzymatic breakdown through fibrin–fibrin cross-linking and cross-linking of fibrinolysis inhibitors, in particular α2-antiplasmin; (ii) the role of intracellular FXIIIa in clot retraction through cross-linking of platelet cytoskeleton proteins, including actin, myosin, filamin and vinculin; (iii) the role of intracellular FXIIIa in cross-linking the cytoplasmic tails of monocyte AT1Rs (angiotensin type 1 receptors) and potential effects on the development of atherosclerosis; and (iv) the role of FXIIIa on matrix deposition and tissue repair, including cross-linking of extracellular matrix proteins, such as fibronectin, collagen and von Willebrand factor, and the effects on matrix deposition and cell–matrix interactions. The review highlights the central role of FXIIIa in the regulation of thrombus stability, thrombus regulation, cell–matrix interactions and wound healing, which is supported by observations in FXIII-deficient humans and animals.

scholarly journals 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

2000 ◽  
Vol 11 (10) ◽  
pp. 3353-3364 ◽  
Author(s):  
Zhantao Yang ◽  
Themis R. Kyriakides ◽  
Paul Bornstein
Keyword(s):  
Molecular Mechanisms ◽  
Fold Increase ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Matrix Metalloproteinase 2 ◽  
Wild Type ◽  
Matricellular Proteins ◽  
Altered Expression ◽  
Cell Matrix ◽  
Matrix Interactions ◽  
Cell Matrix Interactions

Thrombospondin 2 (TSP2)-null mice, generated by disruption of theThbs2 gene, display a variety of connective tissue abnormalities, including fragile skin and the presence of abnormally large collagen fibrils with irregular contours in skin and tendon. In this study we demonstrate that TSP2-null skin fibroblasts show a defect in attachment to a number of matrix proteins, and a reduction in cell spreading. To investigate the molecular mechanisms responsible for these abnormal cell–matrix interactions, we compared the levels of matrix metalloproteinases (MMPs) in wild-type and mutant fibroblasts. Isolation and analysis of gelatinases from conditioned media by gelatin-agarose affinity chromatography and gelatinolytic assays demonstrated that TSP2-null fibroblasts produce a 2-fold increase in gelatinase A (MMP2) compared with wild-type cells. The adhesive defect was corrected by treatment of TSP2-null fibroblasts with soluble TSP2, with the MMP inhibitors BB94 and tissue inhibitor of metalloproteinase-2, and with a neutralizing antibody to MMP2. Moreover, stable transfection of TSP2-null fibroblasts with mouse TSP2 cDNA corrected both the adhesive defect and the altered expression of MMP2. Finally, MMP2 was shown to interact with TSP2 in a direct-binding plate assay. We conclude that TSP2 plays an important role in cell–matrix interactions, and that a deficiency in the protein results in increased levels of MMP2 that contribute to the adhesive defect in TSP2-null fibroblasts and could play a role in the complex phenotype of TSP2-null mice.

International hermelin brain tumor symposium on matricellular proteins in normal and cancer cell-matrix interactions

2004 ◽  
Vol 23 (1) ◽  
pp. 63-69 ◽  
Author(s):  
T.J Bos ◽  
S.L Cohn ◽  
J Koblinski ◽  
H.K Kleinman ◽  
J.E Murphy-Ullrich ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Cancer Cell ◽  
Matricellular Proteins ◽  
Cell Matrix ◽  
Matrix Interactions ◽  
Cell Matrix Interactions

scholarly journals MATHEMATICAL MODELS FOR CELL-MATRIX INTERACTIONS DURING DERMAL WOUND HEALING

2002 ◽  
Vol 12 (09) ◽  
pp. 2021-2029 ◽  
Author(s):  
P. K. MAINI ◽  
L. OLSEN ◽  
J. A. SHERRATT
Keyword(s):  
Wound Healing ◽  
Tumour Growth ◽  
Cell Interaction ◽  
Dermal Wound Healing ◽  
Cell Matrix ◽  
Extracellular Matrix Components ◽  
Matrix Interactions ◽  
Matrix Components ◽  
Cell Matrix Interactions ◽  
Dermal Wound

This paper contains a review of our recent work on the mathematical modeling of cell interaction with extracellular matrix components during the process of dermal wound healing. The models are of partial differential equation type and allow us to investigate in detail how various mechanochemical effects may be responsible for certain wound healing disorders such as fibrocontractive and fibroproliferative diseases. We also present a model for wound healing angiogenesis. The latter has several features in common with angiogenesis during cancer tumour growth and spread so a deeper understanding of the phenomenon in the context of wound healing may also help in the treatment of certain cancers.

scholarly journals Cell-matrix interactions modulate interstitial collagenase expression by human keratinocytes actively involved in wound healing.

1993 ◽  
Vol 92 (6) ◽  
pp. 2858-2866 ◽  
Author(s):  
U K Saarialho-Kere ◽  
S O Kovacs ◽  
A P Pentland ◽  
J E Olerud ◽  
H G Welgus ◽  
...  
Keyword(s):  
Wound Healing ◽  
Human Keratinocytes ◽  
Cell Matrix ◽  
Matrix Interactions ◽  
Cell Matrix Interactions ◽  
Interstitial Collagenase
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