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Asian Pacific Journal of Cancer... 2014Matrix metalloproteinases (MMPs) are a family of zinc dependent extracellular matrix (ECM) remodelling endopeptidases having the ability to degrade almost all components... (Review)
Review
Matrix metalloproteinases (MMPs) are a family of zinc dependent extracellular matrix (ECM) remodelling endopeptidases having the ability to degrade almost all components of extracellular matrix and implicated in various physiological as well as pathological processes. Carcinogenesis is a multistage process in which alteration of the microenvironment is required for conversion of normal tissue to a tumour. Extracellular matrix remodelling proteinases such as MMPs are principal mediators of alterations observed in the microenvironment during carcinogenesis and according to recent concepts not only have roles in invasion or late stages of cancer but also in regulating initial steps of carcinogenesis in a favourable or unfavourable manner. Establishment of relationships between MMP overproduction and cancer progression has stimulated the development of inhibitors that block proteolytic activity of these enzymes. In this review we discuss the MMP general structure, classification, regulation roles in relation to hallmarks of cancer and as targets for therapeutic intervention.
Topics: Apoptosis; Carcinogenesis; Extracellular Matrix; Humans; Matrix Metalloproteinase Inhibitors; Matrix Metalloproteinases; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasms; Neovascularization, Pathologic; Protein Structure, Tertiary; Transcriptional Activation; Tumor Microenvironment
PubMed: 24606423
DOI: 10.7314/apjcp.2014.15.3.1085 -
Journal of the American Podiatric... Jan 2002The structure, classification, function, and regulation of matrix metalloproteinases in normal and abnormal wound healing is discussed. Results from key studies suggest... (Review)
Review
The structure, classification, function, and regulation of matrix metalloproteinases in normal and abnormal wound healing is discussed. Results from key studies suggest that neutrophil-derived matrix metalloproteinase 8 (MMP-8) is the predominant collagenase present in normal healing wounds, and that overexpression and activation of this collagenase may be involved in the pathogenesis of nonhealing chronic leg ulcers. Excessive collagenolytic activity in these chronic wounds is possible because of the reduced levels of tissue inhibitor metalloproteinase 1 (TIMP-1). However, until recently, there have been no studies evaluating levels of matrix metalloproteinase or tissue inhibitors of metalloproteinase activity in chronic diabetic foot wounds. Improving basic knowledge and pharmaceutical intervention in this area ultimately may help clinicians identify and proactively intervene in an effort to prevent normal wounds from becoming chronic. This may prevent the high prevalence of morbidity associated with this significant health problem.
Topics: Humans; Matrix Metalloproteinases; Sensitivity and Specificity; Structure-Activity Relationship; Wound Healing
PubMed: 11796794
DOI: 10.7547/87507315-92-1-12 -
The Journal of Biological Chemistry Dec 1999Five genes potentially encoding novel matrix metalloproteinases (MMPs) have been identified on the Arabidopsis thaliana data base. The predicted proteins have a similar...
Five genes potentially encoding novel matrix metalloproteinases (MMPs) have been identified on the Arabidopsis thaliana data base. The predicted proteins have a similar domain structure to mammalian MMP-7, with a propeptide and catalytic domain but no C-terminal hemopexin-like domain. Four of the A. thaliana MMPs (At-MMPs) have a predicted C-terminal transmembrane domain. The At-MMPs are differentially expressed in flower, leaf, root, and stem tissues from 14-day-old plants. The cDNA for one of the At-MMPs (At1-MMP) was cloned and expressed in Escherichia coli. Following refolding and purification, the proenzyme At1-MMP was shown to undergo autolytic activation in the presence of an organomercurial with a concomitant decrease in M(r). In contrast to this, trypsin-treatment led to the formation of an inactive product. The activated At1-MMP digested myelin basic protein, but was unable to digest gelatin or casein. Three peptide substrates for MMPs were also cleaved by At1-MMP. The enzyme activity of At1-MMP was inhibited by human tissue inhibitors of metalloproteinases 1 and 2 and the hydroxamate inhibitor BB-94.
Topics: Amino Acid Sequence; Arabidopsis; Base Sequence; Databases, Factual; Electrophoresis, Polyacrylamide Gel; Gene Expression; Humans; Matrix Metalloproteinase 3; Matrix Metalloproteinase Inhibitors; Matrix Metalloproteinases; Molecular Sequence Data; Myelin Basic Protein; Phenylalanine; Reverse Transcriptase Polymerase Chain Reaction; Sequence Homology, Amino Acid; Thiophenes; Tissue Inhibitor of Metalloproteinases
PubMed: 10574937
DOI: 10.1074/jbc.274.49.34706 -
Clinical Chemistry and Laboratory... Feb 2004Matrix metalloproteinases (MMPs), also called matrixins, are proteinases that participate in extracellular matrix remodelling and degradation. Under normal physiological... (Review)
Review
Matrix metalloproteinases (MMPs), also called matrixins, are proteinases that participate in extracellular matrix remodelling and degradation. Under normal physiological conditions, the activities of MMPs are precisely regulated at the level of transcription, of activation of the pro-MMP precursor zymogens and of inhibition by endogenous inhibitors (tissue inhibitors of metalloproteinases; TIMPs). Alteration in the regulation of MMP activity is implicated in diseases such as cancer, fibrosis, arthritis and atherosclerosis. The pathological effects of MMPs and TIMPs in cardiovascular diseases involve vascular remodelling, atherosclerotic plaque instability and left ventricular remodelling after myocardial infarction. Since excessive tissue remodelling and increased matrix metalloproteinase activity have been demonstrated during atherosclerotic lesion progression (including plaque disruption), MMPs represent a potential target for therapeutic intervention aimed at modification of vascular pathology by restoring the physiological balance between MMPs and TIMPs. This review describes the members of the MMP and TIMP families and discusses the structure, function and regulation of MMP activity; finally, pharmacological approaches to MMP inhibition are highlighted.
Topics: Animals; Antineoplastic Agents; Arteriosclerosis; Enzyme Inhibitors; Humans; Inflammation; Matrix Metalloproteinase Inhibitors; Matrix Metalloproteinases; Tissue Inhibitor of Metalloproteinases
PubMed: 15061349
DOI: 10.1515/CCLM.2004.024 -
Pulmonary Medicine 2022Tissue inhibitors of matrix metalloproteinases (TIMP) are a family of four endogenous proteins that primarily function to inhibit the activities of proteases such as the... (Review)
Review
Tissue inhibitors of matrix metalloproteinases (TIMP) are a family of four endogenous proteins that primarily function to inhibit the activities of proteases such as the matrix metalloproteinases (MMP). Altered MMP/TIMP ratios are frequently observed in several human diseases. During aging and disease progression, the extracellular matrix (ECM) undergoes structural changes in which elastin and collagens serve an essential role. MMPs and TIMPs significantly influence the ECM. Classically, elevated levels of TIMPs are suggested to result in ECM accumulation leading to fibrosis, whereas loss of TIMP responses leads to enhanced matrix proteolysis. Here, we outline the known roles of the most abundant TIMP, TIMP2, in pulmonary diseases but also discuss future perspectives in TIMP2 research that could impact the lungs. TIMP2 directly inhibits MMPs, in particular MMP2, but TIMP2 is also required for the activation of MMP2 through its interaction with MMP14. The protease and antiprotease imbalance of MMPs and TIMPs are extensively studied in diseases but recent discoveries suggest that TIMPs, specifically, TIMP2 could play other roles in aging and inflammation processes.
Topics: Humans; Tissue Inhibitor of Metalloproteinase-2; Matrix Metalloproteinase 2; Tissue Inhibitor of Metalloproteinases; Matrix Metalloproteinases; Lung; Biology
PubMed: 36624735
DOI: 10.1155/2022/3632764 -
BMC Research Notes Jan 2021Matrix metalloproteinases (MMPs) are important regulators of vascular and uterine remodeling. They exhibit proteolytic activity implicating the efficiency of trophoblast...
OBJECTIVE
Matrix metalloproteinases (MMPs) are important regulators of vascular and uterine remodeling. They exhibit proteolytic activity implicating the efficiency of trophoblast invasion to the uterine wall involving marked hemodynamic and uterine changes. In this pilot study sera of 13 women with normal pregnancy was analyzed to evaluate the usage of MMPs as diagnostic tool. The concentrations of circulating MMP-9, MMP-2/TIMP-2 complex and TIMP-1 in different time points during normal pregnancy has not been studied. The serum levels of MMP-9, TIMP-1, TIMP-2 and MMP-2/TIMP-2 complex were determined by enzyme-linked immunosorbent assay (ELISA). Using the same method, we have shown that serum MMPs are elevated in spontaneous early pregnancy failure as compared to normal pregnancy.
RESULTS
The serum levels of MMP-9 and TIMP-1 were stable throughout pregnancy. The level of MMP-2/TIMP-2 complex was slightly increased after week 15 without statistical significance. For our best knowledge, this is a first study of the serum levels of MMP-9, MMP-2/TIMP-2 and TIMP-1 on different time points during normal pregnancy. Further measurements with the correlation to the outcome of the pregnancy are needed.
Topics: Female; Humans; Matrix Metalloproteinase 2; Matrix Metalloproteinase 3; Matrix Metalloproteinase 9; Matrix Metalloproteinases; Pilot Projects; Pregnancy; Tissue Inhibitor of Metalloproteinase-1; Tissue Inhibitor of Metalloproteinase-2
PubMed: 33482846
DOI: 10.1186/s13104-021-05442-w -
The Journal of Cell Biology Apr 2016Migratory cells translocate membrane type-1 matrix metalloproteinase (MT1-MMP) to podosomes or invadosomes to break extracellular matrix barriers. In this issue, El...
Migratory cells translocate membrane type-1 matrix metalloproteinase (MT1-MMP) to podosomes or invadosomes to break extracellular matrix barriers. In this issue, El Azzouzi et al. (2016.J. Cell. Biol.http://dx.doi.org/10.1083/jcb.201510043) describe an unexpected function for the MT1-MMP cytoplasmic domain in imprinting spatial memory for podosome reformation via assembly in membrane islets.
Topics: Cell Movement; Cytoplasm; Extracellular Matrix; Humans; Matrix Metalloproteinase 14; Matrix Metalloproteinases; Podosomes; Protein Structure, Tertiary
PubMed: 27069020
DOI: 10.1083/jcb.201603066 -
Methods in Molecular Biology (Clifton,... 2017Matrix metalloproteinases (MMPs) are proteolytic enzymes that degrade various components of the extracellular matrix (ECM) and play a role in tissue remodeling. Changes...
Matrix metalloproteinases (MMPs) are proteolytic enzymes that degrade various components of the extracellular matrix (ECM) and play a role in tissue remodeling. Changes in MMPs have been observed in cancer, connective tissue disorders, and vascular disease, and both endogenous tissue inhibitors of MMPs (TIMPs) and synthetic MMP inhibitors (MMPIs) have been evaluated as modulators of MMP activity in various biological systems. Zymography is a simple technique that is commonly used to assess MMP activity and the efficacy of MMPIs. Also, reverse zymography is a modified technique to study the activity of endogenous TIMPs. However, problems are often encountered during the zymography procedure, which could interfere with accurate assessment of MMP activity in control specimens, and thus make it difficult to determine the pathological changes in MMPs and their responsiveness to MMPIs. Simplified protocols for preparation of experimental solutions, tissue preparation, regular and reverse zymography procedures, and zymogram analysis are presented. Additional helpful tips to troubleshoot problems in the zymography technique and to enhance the quality of the zymograms should make it more feasible to determine the changes in MMPs and assess the efficacy of MMPIs in modulating MMP activity in various biological systems and pathological conditions.
Topics: Animals; Electrophoresis, Polyacrylamide Gel; Enzyme Assays; Extracellular Matrix; Female; Humans; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Matrix Metalloproteinases; Rats; Tissue Inhibitor of Metalloproteinases; Uterus
PubMed: 28608202
DOI: 10.1007/978-1-4939-7111-4_8 -
International Journal of Experimental... Oct 2015Matrix metalloproteinases (MMPs), myofibroblasts (MFs) and epithelial proliferation have key roles in neoplastic progression. In this study immunoexpression of MMP-1,...
Immunohistochemical expression of matrix metalloproteinase-1, matrix metalloproteinase-2 and matrix metalloproteinase-9, myofibroblasts and Ki-67 in actinic cheilitis and lip squamous cell carcinoma.
Matrix metalloproteinases (MMPs), myofibroblasts (MFs) and epithelial proliferation have key roles in neoplastic progression. In this study immunoexpression of MMP-1, MMP-2 and MMP-9, presence of MFs and the epithelial proliferation index were investigated in actinic cheilitis (AC), lip squamous cell carcinoma (LSCC) and mucocele (MUC). Thirty cases of AC, thirty cases of LSCC and twenty cases of MUC were selected for immunohistochemical investigation of the proteins MMP-1, MMP-2, MMP-9, α-smooth muscle actin (α-SMA) and Ki-67. The MMP-1 expression in the epithelial component was higher in the AC than the MUC and LSCC. In the connective tissue, the expression was higher in the LSCC. MMP-2 showed lower epithelial and stromal immunostaining in the LSCC when compared to the AC and MUC. The epithelial staining for MMP-9 was higher in the AC when compared to the LSCC. However, in the connective tissue, the expression was lower in the AC compared to other lesions. The cell proliferation rate was increased in proportion to the severity of dysplasia in the AC, while in the LSCC it was higher in well-differentiated lesions compared to moderately differentiated. There were no statistically significant differences in number of MFs present in the lesions studied. The results suggest that MMPs could affect the biological behaviour of ACs and LSCCs inasmuch as they could participate in the development and progression from premalignant lesions to malignant lesions.
Topics: Carcinoma, Squamous Cell; Cheilitis; Humans; Immunohistochemistry; Ki-67 Antigen; Lip Neoplasms; Matrix Metalloproteinase 1; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Matrix Metalloproteinases; Myofibroblasts; Precancerous Conditions
PubMed: 26515234
DOI: 10.1111/iep.12140 -
Respiratory Research 2001Despite much information on their catalytic properties and gene regulation, we actually know very little of what matrix metalloproteinases (MMPs) do in tissues. The... (Review)
Review
Despite much information on their catalytic properties and gene regulation, we actually know very little of what matrix metalloproteinases (MMPs) do in tissues. The catalytic activity of these enzymes has been implicated to function in normal lung biology by participating in branching morphogenesis, homeostasis, and repair, among other events. Overexpression of MMPs, however, has also been blamed for much of the tissue destruction associated with lung inflammation and disease. Beyond their role in the turnover and degradation of extracellular matrix proteins, MMPs also process, activate, and deactivate a variety of soluble factors, and seldom is it readily apparent by presence alone if a specific proteinase in an inflammatory setting is contributing to a reparative or disease process. An important goal of MMP research will be to identify the actual substrates upon which specific enzymes act. This information, in turn, will lead to a clearer understanding of how these extracellular proteinases function in lung development, repair, and disease.
Topics: Animals; Humans; Lung; Matrix Metalloproteinase 12; Matrix Metalloproteinase 7; Matrix Metalloproteinases; Metalloendopeptidases; Substrate Specificity
PubMed: 11686860
DOI: 10.1186/rr33