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Vascular Health and Risk Management 2016Matrix metalloproteinases (MMPs) are zinc- and calcium-dependent endoproteinases that have the ability to break down extracellular matrix. The large range of MMPs'... (Review)
Review
Matrix metalloproteinases (MMPs) are zinc- and calcium-dependent endoproteinases that have the ability to break down extracellular matrix. The large range of MMPs' functions widens their spectrum of potential role as activators or inhibitors in tissue remodeling, cardiovascular diseases, and obesity. In particular, MMP-1, -2, and -9 may be associated with exercise and obesity. Thus, the current study reviewed the effects of different types of exercise (resistance and aerobic) on MMP-1, -2, and -9. Previous studies report that the response of MMP-2 and -9 to resistance exercise is dependent upon the length of exercise training, since long-term resistance exercise training increased both MMP-2 and -9, whereas acute bout of resistance exercise decreased these MMPs. Aerobic exercise produces an inconsistent result on MMPs, although some studies showed a decrease in MMP-1. Obesity is related to a relatively lower level of MMP-9, indicating that an exercise-induced increase in MMP-9 may positively influence obesity. A comprehensive understanding of the relationship between exercise, obesity, and MMPs does not exist yet. Future studies examining the acute and chronic responses of these MMPs using different subject models may provide a better understanding of the molecular mechanisms that are associated with exercise, obesity, and cardiovascular disease.
Topics: Animals; Collagenases; Enzyme Activation; Exercise; Humans; Matrix Metalloproteinase 1; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Matrix Metalloproteinases, Secreted; Obesity; Tissue Inhibitor of Metalloproteinases
PubMed: 27471391
DOI: 10.2147/VHRM.S103877 -
International Journal of Molecular... Aug 2022This review article aims to describe some of the roles of Matrix metalloproteinases (MMPs) in enamel, dentine, dental caries, hybrid layer degradation, pulp and... (Review)
Review
OBJECTIVES
This review article aims to describe some of the roles of Matrix metalloproteinases (MMPs) in enamel, dentine, dental caries, hybrid layer degradation, pulp and periodontal tissues, throwing light on their current inhibitors. The article addresses the potential of MMPs to serve as biomarkers with diagnostic and therapeutic value.
DESIGN
The sections of this review discuss MMPs' involvement in developmental, remodeling, degradational and turnover aspects of dental and periodontal tissues as well as their signals in the pathogenesis, progress of different lesions and wound healing of these tissues. The literature was searched for original research articles, review articles and theses. The literature search was conducted in PubMed and MEDLINE for articles published in the last 20 years.
RESULTS
119 published papers, two textbooks and two doctoral theses were selected for preparing the current review.
CONCLUSIONS
MMPs are significant proteases, of evident contribution in dental and periapical tissue development, health and disease processes, with promising potential for use as diagnostic and prognostic disease biomarkers. Continuing understanding of their role in pathogenesis and progress of different dental, periapical and periodontal lesions, as well as in dentine-pulp wound healing could be a keystone to future diagnostic and therapeutic regimens.
Topics: Biomarkers; Dental Caries; Humans; Matrix Metalloproteinases; Periodontium
PubMed: 36012195
DOI: 10.3390/ijms23168929 -
Romanian Journal of Morphology and... 2007Matrix metalloproteinases (MMPs) occupy a central role in embryogenesis and in normal physiological conditions, such as proliferation, cell motility, remodeling, wound... (Review)
Review
Matrix metalloproteinases (MMPs) occupy a central role in embryogenesis and in normal physiological conditions, such as proliferation, cell motility, remodeling, wound healing, angiogenesis, and key reproductive events. MMPs form a multigenic family of proteolytic, zinc-dependent enzymes, with 26 members described until present, displaying multidomain structures and substrate specificities. MMPs are involved in both the turnover and degradation of extracellular matrix (ECM) proteins and in the processing, activation, or deactivation of a variety of soluble factors. They are regulated at the level of transcription, activation of the precursor zymogens, and inhibition mainly by tissue inhibitors of metalloproteinases (TIMPs). Any loss in activity control may result in various diseases. This review provides an update of biological functions of MMPs, facilitating the understanding of the complex pathogenic mechanisms of medical conditions characterized by imbalance between MMP and TIMP expression. The design of potent specific inhibitors for MMPs represents a scientific challenge for the development of new therapies.
Topics: Chromosome Mapping; Chromosomes, Human; Gelatinases; Humans; Matrix Metalloproteinase 3; Matrix Metalloproteinase 7; Matrix Metalloproteinases; Protein Conformation
PubMed: 18060181
DOI: No ID Found -
Molecular Aspects of Medicine Oct 2008Matrix metalloproteinases (MMPs) are now acknowledged as key players in the regulation of both cell-cell and cell-extracellular matrix interactions. They are involved in... (Review)
Review
Matrix metalloproteinases (MMPs) are now acknowledged as key players in the regulation of both cell-cell and cell-extracellular matrix interactions. They are involved in modifying matrix structure, growth factor availability and the function of cell surface signalling systems, with consequent effects on cellular differentiation, proliferation and apoptosis. They play central roles in morphogenesis, wound healing, tissue repair and remodelling in response to injury and in the progression of diseases such as arthritis, cancer and cardiovascular disease. Because of their wide spectrum of activities and expression sites, the elucidation of their potential as drug targets in disease or as important features of the repair process will be dependent upon careful analysis of their role in different cellular locations and at different disease stages. Novel approaches to the specific regulation of individual MMPs in different contexts are also being developed.
Topics: Animals; Arthritis; Extracellular Matrix; Humans; Matrix Metalloproteinase Inhibitors; Matrix Metalloproteinases; Models, Molecular; Neoplasms; Protein Conformation; Substrate Specificity; Tissue Inhibitor of Metalloproteinases; Vascular Diseases
PubMed: 18619669
DOI: 10.1016/j.mam.2008.05.002 -
International Journal of Molecular... Mar 2023Endometrial and cervical cancers are the two most common gynaecological malignancies and among the leading causes of death worldwide. The extracellular matrix (ECM) is... (Review)
Review
Endometrial and cervical cancers are the two most common gynaecological malignancies and among the leading causes of death worldwide. The extracellular matrix (ECM) is an important component of the cellular microenvironment and plays an important role in developing and regulating normal tissues and homeostasis. The pathological dynamics of the ECM contribute to several different processes such as endometriosis, infertility, cancer, and metastasis. Identifying changes in components of ECM is crucial for understanding the mechanisms of cancer development and its progression. We performed a systematic analysis of publications on the topic of changes in the extracellular matrix in cervical and endometrial cancer. The findings of this systematic review show that matrix metalloproteinases (MMP) play an important role impacting tumour growth in both types of cancer. MMPs degrade various specific substrates (collagen, elastin, fibronectin, aggrecan, fibulin, laminin, tenascin, vitronectin, versican, nidogen) and play a crucial role in the basal membrane degradation and ECM components. Similar types of MMPs were found to be increased in both cancers, namely, MMP-1, MMP-2, MMP-9, and MMP-11. Elevated concentrations of MMP-2 and MMP-9 were correlated with the FIGO stage and are associated with poor prognosis in endometrial cancer, whereas in cervical cancer, elevated concentrations of MMP-9 have been associated with a better outcome. Elevated ADAMTS levels were found in cervical cancer tissues. Elevated disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) levels were also found in endometrial cancer, but their role is still unclear. Following these findings, this review reports on tissue inhibitors of ECM enzymes, MMPs, and ADAMTS. The present review demonstrates changes in the extracellular matrix in cervical and endometrial cancers and compared their effect on cancer development, progression, and patient prognosis.
Topics: Female; Humans; Uterine Cervical Neoplasms; Matrix Metalloproteinase 9; Matrix Metalloproteinase 2; Extracellular Matrix; Matrix Metalloproteinases; Endometrial Neoplasms; Tumor Microenvironment
PubMed: 36982551
DOI: 10.3390/ijms24065463 -
Biochimica Et Biophysica Acta.... Nov 2017Water soluble matrix metalloproteinases (MMPs) have been regarded as diffusing freely in the extracellular matrix. Yet multiple MMPs are also observed at cell surfaces.... (Review)
Review
Water soluble matrix metalloproteinases (MMPs) have been regarded as diffusing freely in the extracellular matrix. Yet multiple MMPs are also observed at cell surfaces. Their membrane-proximal activities include sheddase activities, collagenolysis, bacterial killing, and intracellular trafficking reaching as far as the nucleus. The catalytic domains of MMP-7 and MMP-12 bind bilayers peripherally, each in two different orientations, by presenting positive charges and a few hydrophobic groups to the surface. Related peripheral membrane associations are predicted for other soluble MMPs. The peripheral membrane associations may support pericellular proteolysis and endocytosis. The isolated soluble domains of MT1-MMP can also associate with membranes. NMR assays suggest transient association of the hemopexin-like domains of MT1-MMP and MMP-12 with lipid bilayers. Peripheral association of soluble MMP domains with bilayers or heparin sulfate proteoglycans probably concentrates them near the membrane. This could increase the probability of forming complexes with membrane-associated proteins, such as those targeted for proteolysis. This article is part of a Special Issue entitled: Matrix Metalloproteinases edited by Rafael Fridman.
Topics: Animals; Cell Membrane; Heparin; Humans; Matrix Metalloproteinase 12; Matrix Metalloproteinase 14; Matrix Metalloproteinase 7; Nuclear Magnetic Resonance, Biomolecular; Protein Domains; Proteoglycans; Proteolysis
PubMed: 28442379
DOI: 10.1016/j.bbamcr.2017.04.013 -
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 -
Biochimica Et Biophysica Acta.... Nov 2017Inflammation is a central mechanism for dealing with insults to tissue, either from pathogenic invaders or by other damage-inducing means, such that the threat is... (Review)
Review
Inflammation is a central mechanism for dealing with insults to tissue, either from pathogenic invaders or by other damage-inducing means, such that the threat is removed, the tissue is healed and there is a return to homeostasis. It is a multi-step process with manifold methods of regulation built in. Proteolysis is one such regulatory method and members of the matrix metalloproteinase (MMP) family of proteinases have been shown to influence inflammation in myriad of ways. It is becoming more and more clear that no single MMP can be unequivocally labeled as 'good' or 'bad' when considering inflammation in general - the net result of proteolytic activity is dependent on context. Here we provide examples from recent literature, with a focus on in vivo studies, to highlight this concept. This article is part of a Special Issue entitled: Matrix Metalloproteinases edited by Rafael Fridman.
Topics: Animals; Humans; Inflammation; Matrix Metalloproteinases; Proteolysis
PubMed: 28502592
DOI: 10.1016/j.bbamcr.2017.05.010 -
Scientific Reports May 2023To better clarify the causal effects between matrix metalloproteinases (MMPs) and estrogen-receptor (ER)-negative breast cancer (BC), we investigated the bidirectional...
To better clarify the causal effects between matrix metalloproteinases (MMPs) and estrogen-receptor (ER)-negative breast cancer (BC), we investigated the bidirectional causal relationship between MMPs and ER-negative BC by mendelian randomization (MR) analysis. Summary statistic data of five MMPs were extracted from European participants in 13 cohorts. Data of ER-negative BC collected from one of genome-wide association studies of European ancestry was used as experimental datasets and another four ER-negative BC datasets were used as validation sets. Inverse variance weighted method was used for main MR analysis and sensitivity analysis was also conducted. Serum level of MMP-1 has negative effect on ER-negative BC (odds ratio = 0.92, P = 0.0008) but the latter one was not the cause of the former one, which was supported by validation sets. No bidirectional causal effect was detected between the other four types of MMPs and ER-negative BC (P > 0.05). Sensitivity analysis indicated robustness of the above results without remarkable bias. To conclude, serum MMP-1 may be a protective factor against ER-negative BC. No reciprocal causality was found between the other kinds of MMPs and ER-negative BC. MMP-1 was indicated as a biomarker for risk of ER-negative BC.
Topics: Humans; Genome-Wide Association Study; Matrix Metalloproteinase 1; Mendelian Randomization Analysis; Receptors, Estrogen; Triple Negative Breast Neoplasms; Matrix Metalloproteinases
PubMed: 37188722
DOI: 10.1038/s41598-023-34200-0 -
Biochimica Et Biophysica Acta Jan 2010
Topics: Animals; Clinical Trials as Topic; Humans; Matrix Metalloproteinase Inhibitors; Matrix Metalloproteinases; Neoplasms; Protease Inhibitors; Substrate Specificity
PubMed: 20159302
DOI: 10.1016/j.bbamcr.2010.01.016