-
Seminars in Ophthalmology Nov 2023Matrix metalloproteinases (MMPs) are important regulators of the extracellular matrix (ECM) and are involved in many stages of cellular growth and development. An... (Review)
Review
Matrix metalloproteinases (MMPs) are important regulators of the extracellular matrix (ECM) and are involved in many stages of cellular growth and development. An imbalance of MMP expression is also the basis of many diseases, including eye diseases, such as diabetic retinopathy (DR), glaucoma, dry eye, corneal ulcer, keratoconus. This paper describes the role of MMPs in the glaucoma and their role in the glaucomatous trabecular meshwork (TM), aqueous outflow channel, retina, and optic nerve (ON). This review also summarizes several treatments for glaucoma that target MMPs imbalance and suggests that MMPs may represent a viable therapeutic target for glaucoma.
Topics: Humans; Intraocular Pressure; Glaucoma; Trabecular Meshwork; Extracellular Matrix; Matrix Metalloproteinases; Aqueous Humor
PubMed: 37224230
DOI: 10.1080/08820538.2023.2211149 -
Microvascular Research Sep 2022Vascular diseases are the main cause of morbidity and mortality. The vascular extracellular matrix (ECM) is essential in mechanical support, also regulating the cellular... (Review)
Review
Vascular diseases are the main cause of morbidity and mortality. The vascular extracellular matrix (ECM) is essential in mechanical support, also regulating the cellular behavior fundamental to vascular function and homeostasis. Vascular remodeling is an adaptive response to various physiological and pathological changes and is associated with aging and vascular diseases. The aim of this review is provide a general overview of the involvement of MMPs in the pathogenesis of vascular diseases, namely, arterial hypertension, atherosclerosis, aortic aneurysms and myocardial infarction. The change in the composition of the ECM by matrix metalloproteinases (MMPs) generates a pro-inflammatory microenvironment that modifies the phenotypes of endothelial cells and vascular smooth muscle cells. They play a central role in morphogenesis, tissue repair and remodeling in response to injury, e.g., after myocardial infarction, and in progression of diseases such as atherosclerosis. Alterations in specific MMPs could influence arterial remodeling and lead to various pathological disorders such as hypertension and aneurysm formation. MMPs are regulated by endogenous tissue inhibitors of metalloproteinases (TIMPs), and the MMP/TIMP ratio generally determines the extent of ECM protein degradation and tissue remodeling. Studies are currently focused on improving the diagnostic and prognostic value of MMPs involved in the pathogenic process, increasing their therapeutic potential, and monitoring the disease. New selective MMP inhibitors may improve the specificity of these inhibitors, target specific MMPs in relevant pathological conditions and mitigate some of the side effects.
Topics: Atherosclerosis; Endothelial Cells; Extracellular Matrix; Humans; Hypertension; Matrix Metalloproteinase Inhibitors; Matrix Metalloproteinases; Myocardial Infarction
PubMed: 35671836
DOI: 10.1016/j.mvr.2022.104398 -
Anatomical Record (Hoboken, N.J. : 2007) Jun 2020CD147, also known as extracellular matrix metalloproteinase inducer (EMMPRIN) or basigin, is expressed in a variety of cell types. It is involved in the regulation of... (Review)
Review
CD147, also known as extracellular matrix metalloproteinase inducer (EMMPRIN) or basigin, is expressed in a variety of cell types. It is involved in the regulation of extracellular matrix (ECM) remodeling during physiological and pathological processes including wound healing, inflammatory diseases, and cancer. CD147 is a diagnostic and therapeutic target in cancer and inflammatory diseases, either directly or indirectly, by targeting CD147 partners. It can trigger matrix metalloproteinase inductions involved in ECM degradation, cell adhesion, and cell-cell interactions. It can also induce myofibroblast differentiation associated with ECM deposition and contraction. The shift from fibrosis to lysis, and vice versa, is poorly understood and could involve CD147. This article provides an overview of the role of CD147 in the regulation of ECM remodeling processes and discusses the involvement of the microenvironment in the modulation of its downstream effects. Understanding CD147 regulation could help identify new therapeutic intervention. Anat Rec, 2019. © 2019 Wiley Periodicals, Inc.
Topics: Animals; Basigin; Cell Differentiation; Extracellular Matrix; Fibroblasts; Humans; Matrix Metalloproteinases; Wound Healing
PubMed: 30768865
DOI: 10.1002/ar.24089 -
Biomedicine & Pharmacotherapy =... May 2023Liver fibrosis is the common consequence of various chronic liver injuries and is mainly characterized by the imbalance between the production and degradation of... (Review)
Review
Liver fibrosis is the common consequence of various chronic liver injuries and is mainly characterized by the imbalance between the production and degradation of extracellular matrix, which leads to the accumulation of interstitial collagen and other matrix components. Matrix metalloproteinases (MMPs) and their specific inhibitors, that is, tissue inhibitors of metalloproteinases (TIMPs), play a crucial role in collagen synthesis and lysis. Previous in vivo and in vitro studies of our laboratory found repressing extracellular matrix (ECM) accumulation by restoring the balance between MMPs and TIMPs can alleviate liver fibrosis. We conducted a review of articles published in PubMed and Science Direct in the last decade until February 1, 2023, which were searched for using these words "MMPs/TIMPs" and "Hepatic Fibrosis." Through a literature review, this article reviews the experimental studies of liver fibrosis based on MMPs/TIMPs, summarizes the components that may exert an anti-liver fibrosis effect by affecting the expression or activity of MMPs/TIMPs, and attempts to clarify the mechanism of MMPs/TIMPs in regulating collagen homeostasis, so as to provide support for the development of anti-liver fibrosis drugs. We found the MMP-TIMP-ECM interaction can result in better understanding of the pathogenesis and progression of hepatic fibrosis from a different angle, and targeting this interaction may be a promising therapeutic strategy for hepatic fibrosis. Additionally, we summarized and analyzed the drugs that have been found to reduce liver fibrosis by changing the ratio of MMPs/TIMPs, including medicine natural products.
Topics: Humans; Collagen; Extracellular Matrix; Liver Cirrhosis; Matrix Metalloproteinases; Tissue Inhibitor of Metalloproteinase-1; Tissue Inhibitor of Metalloproteinases
PubMed: 37002573
DOI: 10.1016/j.biopha.2023.114472 -
Journal of the Neurological Sciences Dec 2020Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the loss of upper and lower motor neurons that results in progressive paralysis and... (Review)
Review
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the loss of upper and lower motor neurons that results in progressive paralysis and muscular atrophy. There are many molecules and genes involved in neuromuscular degeneration in ALS; among these, matrix metalloproteinases (MMPs). MMPs play an important role in the pathology of ALS, and MMP-1, 2, 3, and 9 might serve as disease progression markers. Tissue inhibitors of metalloproteinases (TIMPS) might also function as progression markers in ALS because they participate in regulating the proteolytic activity of MMPs. Moreover, a diversity of genes also plays a role in the pathogenesis of ALS; most MMPs-coding genes present variants related to the pathological proteolytic activity. This short review, however, will focus on the role of matrix metalloproteinases in ALS.
Topics: Amyotrophic Lateral Sclerosis; Humans; Matrix Metalloproteinases; Motor Neurons; Neurodegenerative Diseases
PubMed: 33068904
DOI: 10.1016/j.jns.2020.117175 -
Current Pharmaceutical Design 2021Cancer is a wide range cellular level disease that occurs when cells go through uncontrolled division and growth. The mechanisms by which the cells undergo metastasis... (Review)
Review
BACKGROUND
Cancer is a wide range cellular level disease that occurs when cells go through uncontrolled division and growth. The mechanisms by which the cells undergo metastasis are complex and involve many interactions between the tumor cells and their cellular environment. Matrix metalloproteinases (MMPs) have been found to over-express at various stages of tumor progression and their inhibition using MMP inhibitors has been a subject of potential therapy against cancer.
OBJECTIVE
This review discusses recent research in MMP inhibitors (MMPI) used for preventing tumor progression.
METHODS
In this review, we explored the role of MMPs in cancer progression and summarized the current developments in MMPIs, their role in cancer suppression in in vitro and in vivo studies and their evaluation in clinical trials from the current research data.
RESULTS
MMPIs have shown to be very successful in in vitro models, cell lines and in some in vivo studies. Unfortunately, their efficacy in clinical trials has been found to be hit and miss. Recent studies have shown that the novel delivery approaches of MMP inhibitors may enhance their therapeutic effects towards the prevention of cancer.
CONCLUSION
In this review, we presented different MMP inhibitors, their performance at different stages of models - in vitro, in vivo, small animal models and eventually clinical trials. We provide newer methods of MMPI delivery that may be better targeted to suppress only specific MMPs and avoid toxic side effects in healthy cells.
Topics: Animals; Antineoplastic Agents; Humans; Matrix Metalloproteinase Inhibitors; Matrix Metalloproteinases; Neoplasms
PubMed: 34459380
DOI: 10.2174/1381612827666210830103059 -
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 -
Molecules (Basel, Switzerland) Apr 2023Matrix metalloproteinase-9 (MMP-9), one of the most investigated and studied biomarkers of the MMPs family, is a zinc-dependent proteolytic metalloenzyme whose primary... (Review)
Review
Matrix metalloproteinase-9 (MMP-9), one of the most investigated and studied biomarkers of the MMPs family, is a zinc-dependent proteolytic metalloenzyme whose primary function is degrading the extracellular matrix (ECM). It has been proved that MMP-9 expression elevates in multiple pathological conditions, including thyroid carcinoma. MMP-9 has a detectable higher level in malignant or metastatic thyroid tumor tissues than in normal or benign tissues and acts as an additional marker to distinguish different tumor stages because of its close correlations with clinical features, such as lymph node metastasis, TNM stage, tumor size and so on. Natural and non-natural MMP-9 inhibitors suppress its expression, block the progression of diseases, and play a role in therapy consequently. MMP-9 inhibitory molecules also assist in treating thyroid tumors by suppressing the proliferation, invasion, migration, metastasis, viability, adhesion, motility, epithelial-mesenchymal transition (EMT), and other risk factors of different thyroid cancer cells. In a word, discovering and designing MMP-9 inhibitors provide great therapeutic effects and promising clinical values in various types of thyroid carcinoma.
Topics: Humans; Matrix Metalloproteinase 9; Thyroid Neoplasms; Matrix Metalloproteinase Inhibitors; Matrix Metalloproteinases
PubMed: 37175113
DOI: 10.3390/molecules28093705 -
Developmental Dynamics : An Official... Feb 2022Membrane-type matrix metalloproteinases (MT-MMPs) are cell membrane-tethered proteinases that belong to the family of the MMPs. Apart from their roles in degradation of... (Review)
Review
Membrane-type matrix metalloproteinases (MT-MMPs) are cell membrane-tethered proteinases that belong to the family of the MMPs. Apart from their roles in degradation of the extracellular milieu, MT-MMPs are able to activate through proteolytic processing at the cell surface distinct molecules such as receptors, growth factors, cytokines, adhesion molecules, and other pericellular proteins. Although most of the information regarding these enzymes comes from cancer studies, our current knowledge about their contribution in distinct developmental processes occurring in the embryo is limited. In this review, we want to summarize the involvement of MT-MMPs in distinct processes during embryonic morphogenesis, including cell migration and proliferation, epithelial-mesenchymal transition, cell polarity and branching, axon growth and navigation, synapse formation, and angiogenesis. We also considered information about MT-MMP functions from studies assessed in pathological conditions and compared these data with those relevant for embryonic development.
Topics: Cell Membrane; Embryonic Development; Extracellular Matrix; Humans; Matrix Metalloproteinases; Matrix Metalloproteinases, Membrane-Associated; Neoplasms
PubMed: 34241926
DOI: 10.1002/dvdy.398 -
Current Pharmaceutical Biotechnology 2021Matrix Metalloproteinases (MMPs), as a family of zinc-containing enzymes, show the function of decomposing Extracellular Matrix (ECM) and participate in the... (Review)
Review
Matrix Metalloproteinases (MMPs), as a family of zinc-containing enzymes, show the function of decomposing Extracellular Matrix (ECM) and participate in the physiological processes of cell migration, growth, inflammation, and metabolism. Clinical and experimental studies have indicated that MMPs play an essential role in tissue injury and repair as well as tumor diagnosis, metastasis, and prognosis. An increasing number of researchers have paid attention to their functions and mechanisms in bone health and diseases. The present review focuses on MMPs-inspired therapeutic strategies for the treatment of bone-related diseases. We introduce the role of MMPs in bone diseases, highlight the MMPs-inspired therapeutic options, and posit MMPs as a trigger for smart cell/drug delivery.
Topics: Animals; Bone Diseases; Extracellular Matrix; Humans; Matrix Metalloproteinases
PubMed: 32603279
DOI: 10.2174/1389201021666200630140735