Metalloproteinases and their inhibitors: regulators of wound healing.

Center for Lung Biology, University of Washington, 815 Mercer Street, Seattle, WA 98109, USA.
The International Journal of Biochemistry & Cell Biology (Impact Factor: 4.24). 02/2008; 40(6-7):1334-47. DOI: 10.1016/j.biocel.2007.10.024
Source: PubMed

ABSTRACT 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.


Available from: Sean E Gill, Aug 14, 2014
  • [Show abstract] [Hide abstract]
    ABSTRACT: Colorectal cancer (CRC) is the third most frequent malignancy. Many factors such as NF-κB, matrix metalloproteinase-1 (MMP-1), p53, and Ki-67 are likely to be involved in its development and progression. Lymph node metastases indicate increased tumor burden and tumor cell heterogeneity and affect both the treatment strategies and the prognosis. In this study, expressions of NF-κB, MMP-1, p53, and Ki-67 were between the primary tumors and lymph node metastases in 110 Dukes’ stage C, CRC cases by immunohistochemical methods, related to patients’ clinical outcomes. NF-κB, p53, and Ki-67 expressions were significantly higher in the metastatic lymph nodes compared to the primary tumor tissues (, , and , resp.). In the metastatic lymph nodes NF-κB expression was correlated with both p53 (, ) and Ki-67 (, ) expressions. The univariant and multivariant analyses showed that only “pT stage” preserved an independent prognostic significance for recurrence-free survival rates and 5-year overall survival rates ( for both). Metastatic cells can acquire different biological characteristics compared to their primaries. Elucidation of properties acquired by metastatic cells is important in order to better determine prognosis, reverse drug resistance, and discover new treatment alternatives.
    Gastroenterology Research and Practice 01/2015; 2015:1-9. DOI:10.1155/2015/945392 · 1.50 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The management of chronic skin wounds represents a major therapeutic challenge. The synthesized dipeptide (Glu-Trp-ONa) and its acylated analogue (R-Glu-Trp-ONa) were assessed in the model of nonhealing dermal wounds in rabbits in relation to their healing properties in wound closure. Following wound modeling, the rabbits received a course of intraperitoneal injections of Glu-Trp-ONa or R-Glu-Trp-ONa. Phosphate-buffered saline and Solcoseryl ® were applied as negative and positive control agents, respectively. An injection of Glu-Trp-ONa and R-Glu-Trp-ONa decreased the period of wound healing in animals in comparison to the control and Solcoseryl-treated groups. Acylation of Glu-Trp-ONa proved to be beneficial as related to the healing properties of the dipeptide. Subsequent zymography analyses showed that the applied peptides decreased the proteolytic activity of matrix metalloproteinases MMP-9, MMP-8, and MMP-2 in the early inflammatory phase and reversely increased the activity of MMP-9, MMP-8, and MMP-1 in the remodeling phase. Histological analyses of the wound sections (hematoxylin–eosin, Mallory's staining) confirmed the enhanced formation of granulation tissue and re-epithelialization in the experimental groups. By administering the peptides, wound closures increased significantly through the modulation of the MMPs' activity, indicating their role in wound healing.
    Drug Design, Development and Therapy 03/2015; 2015:9-1717. DOI:10.2147/DDDT.S79665 · 3.03 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The performance of biomaterials in vivo is largely influenced by their stability and the rate and extent to which they degrade. Materials for tissue engineering applications, for example, have to be mechanically stable to support cell adhesion and proliferation without collapsing. On the other hand they need to be replaced gradually by native extracellular matrix and have to be (slowly) biodegradable. Therefore, it is of critical importance to be able to tune the degradation behavior of a biomaterial. Recombinantly produced spider silk proteins have been shown to be versatile biopolymers for medical applications. They can be processed into a variety of morphologies, and by chemical or genetic modification the properties can be adjusted to specific demands. Furthermore, in vivo experiments confirmed the lack of immunological reactions towards certain spider silks. In this study the degradation behavior of the recombinant spider silk protein eADF4(C16) in solution as well as processed into particles, films and non-woven meshes was analyzed, and the impact of crosslinking of the scaffolds was assessed thereon. In addition to two bacterial proteolytic model enzymes, protease type XIV from Streptomyces griseus (PXIV) and collagenase type IA from Clostridium histolyticum (CHC) used in all experiments, several recombinant human matrix metalloproteinases (MMPs) and one elastase were used in studying degradation of soluble eADF4(C16). For soluble eADF4(C16) all degradation kinetics were similar. In case of eADF4(C16) scaffolds significant differences were observable between PXIV and CHC. All scaffolds were more stable towards proteolytic degradation in the presence of CHC than in the presence of PXIV. Further, particles were degraded significantly faster than films, and non-woven meshes showed the highest proteolytic stability. Chemical crosslinking of the scaffolds led to a decrease in both degradation rate and extent.
    04/2015; 1(4):247-259. DOI:10.1021/ab500147u