Gill, S.E. & Parks, W.C. Metalloproteinases and their inhibitors: regulators of wound healing. Int. J. Biochem. Cell Biol. 40, 1334-1347

Center for Lung Biology, University of Washington, 815 Mercer Street, Seattle, WA 98109, USA.
The International Journal of Biochemistry & Cell Biology (Impact Factor: 4.05). 02/2008; 40(6-7):1334-47. DOI: 10.1016/j.biocel.2007.10.024
Source: PubMed


Wound healing is a dynamic process that involves a coordinated response of many cell types representing distinct tissue compartments and is fundamentally similar among tissue types. Among the many gene products that are essential for restoration of normal tissue architecture, several members of the matrix metalloproteinase (MMP) family function as positive and, at times, negative regulators of repair processes. MMPs were initially thought to only function in the resolution phase of wound healing, particularly during scar resorption; however, recent evidence suggests that they also influence other wound-healing responses, such as inflammation and re-epithelialization. In this review, we discuss what is currently known about the function of MMPs in wound healing and will provide suggestions for future research directions.

Download full-text


Available from: Sean E Gill, Aug 14, 2014
  • Source
    • "The concentration of growth factors and cytokines in PRP are well described, some having correlations with age [7,8]. However, the understanding of the dynamic interplay between cell mediators remains incomplete since matrix metalloproteases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are also found in platelets and affect the activity of growth factors [9]. MMPs are known modulators of the extracellular matrix through the cleavage of growth factor receptors, cause the release of growth factors, independently affect the extracellular matrix, and regulate all phases of wound healing [9,10]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The use of autologous blood concentrates, such as activated, concentrated platelets, in orthopaedic clinical applications has had mixed results. Research on this topic has focused on growth factors and cytokines, with little directed towards matrix metalloproteinases (MMPs) which are involved in post-wound tissue remodeling. In this study, the authors measured the levels of MMP-2, MMP-9 and a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13), in activated platelets derived from blood of healthy, male volunteers (n = 92), 19 to 60 years old. The levels of the natural inhibitors of these proteases, tissue inhibitor of metalloproteinase 1 (TIMP-1), TIMP-2 and TIMP-4 were also assessed. Notably, there was no significant change in concentration with age in four of six targets tested. However, TIMP-2 and TIMP-4 demonstrated a statistically significant increase in concentration for subjects older than 30 years of age compared to those 30 years and younger (P = 0.04 and P = 0.04, respectively). TIMP-2 and TIMP-4 are global inhibitors of MMPs, including MMP-2 (Gelatinase A). MMP-2 targets native collagens, gelatin and elastin to remodel the extracellular matrix during wound healing. A decreased availability of pharmacologically active MMP-2 may diminish the effectiveness of the use of activated, concentrated platelets from older patients, and may also contribute to longer healing times in this population.
    Full-text · Article · Apr 2014 · Journal of Orthopaedic Surgery and Research
  • Source
    • "MMPs degrade the extracellular matrix which is general remodeling process that enables several pathologic conditions including inflammatory, vascular, and autoimmune disorders, and carcinogenesis as well as physiological processes like wound healing, bone resorption, uterine involution , and organogenesis (Egeblad and Werb, 2002; Lee and Murphy, 2004). These endopeptidases are made up of enzymes namely serralysins, astacins, adamalysins (a disintegrin and metalloproteinase domain or ADAMs), and matrixins (MMPs) which are from metzincin family (Gill and Parks, 2008). There are more than 20 enzymes that are broadly classified into 6 groups as shown in Table 1 (Velinov et al., 2010). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Matrix metalloproteinases are endopeptidases which belong to the group of metalloproteinases that contribute for the extra-cellular matrix degradation, and several tissue remodeling processes. An imbalance in the regulation of these endopeptidases eventually leads to several severe pathological complications like cancers, cardiac, cartilage, and neurological related diseases. Hence inhibitory substances of metalloproteinases (MMPIs) could prove beneficial in the management of above specified pathological conditions. The available synthetic MMPIs that have been reported until now have few shortcomings and thus many of them could not make to the final clinical trials. Hence a growing interest among researchers on screening of MMPIs from different natural resources is evident and especially natural products from marine origin. As there has been an unparalleled contribution of several biologically active compounds from marine resources that have shown profound applications in nutraceuticals, cosmeceuticals, and pharmaceuticals, we have attempted to discuss the various MMPIs from edible sea-weeds.
    Full-text · Article · Apr 2014 · Environmental Toxicology and Pharmacology
  • Source
    • "A mildly acute inflammatory reaction attracted a large number of polymorphonuclear leukocytes and some macrophages to clean away debris and blood clots [2]. Also the secretion of cell cytokines and growth factors by these cells provided an excellent environment for wound healing [3] [4]. The migration of fibroblast cells, which was promoted by SACCHACHITIN, also plays another important role in accelerating wound healing [1]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: LUFFACHITIN obtained from the residue of the sponge-like dried fruit of Luffa aegyptiaca was developed as a weavable skin substitute in this study. A chemical analysis revealed that LUFFACHITIN was composed of a copolymer containing N-acetyl-glucosamine (~40%) as a major monomer with a filamentary structure as demonstrated by both optical and scanning electron microscopy. The pulp-like white residue of the sponge-like dried fruit of Luffa aegyptiaca after treatment was then woven into a thin, porous membrane by filtration and lyophilization as a skin substitute for conducting wound-healing study on rats. The results indicated that the LUFFACHITIN membrane showed significant wound-healing enhancement (25 days to complete healing) compared to cotton gauze (>30 days), but not inferior to that of SACCHACHITIN. Furthermore, the LUFFACHITIN membrane had advantages of having a high yield, better physical properties for fabrication, and a more attractive appearance.
    Full-text · Article · Apr 2014
Show more