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FASEB Journal : Official Publication of... Mar 2011Aging impairs function in the nonischemic heart and is associated with mechanical remodeling. This process includes accumulation of collagen (i.e., fibrosis) and...
Aging impairs function in the nonischemic heart and is associated with mechanical remodeling. This process includes accumulation of collagen (i.e., fibrosis) and dysregulation of active matrix metalloproteinases (MMPs). Exercise training (ET) improves cardiac function, but the pathways of protection remain poorly understood. Young (3 mo) and old (31 mo) FBNF1 rats were assigned into sedentary and exercise groups, with ET group rats training on a treadmill 45 min/d, 5 d/wk for 12 wk. Nonlinear optical microscopy (NLOM), histology, immunohistochemistry (IHC), and Western blot analyses were performed on the left ventricle and septum. NLOM, IHC, and histological imaging revealed that ET reduced age-associated elevation of collagen type I fibers. Active MMP-1, active MMP-2, and MMP-14 in the ECM fraction of the left ventricle were reduced by aging, an effect abrogated by ET. Tissue inhibitor of MMP (TIMP-1) was elevated with age but protected by ET. Transforming growth factor-β (TGF-β), upstream regulator of TIMP-1, increased with age but was attenuated by ET. Therefore, exercise training could protect the aging heart against dysregulation of MMPs and fibrosis by suppressing elevation of TIMP-1 and TGF-β.
Topics: Aging; Animals; Fibrosis; Heart Diseases; Matrix Metalloproteinase 1; Matrix Metalloproteinase 14; Matrix Metalloproteinase 2; Matrix Metalloproteinase 3; Matrix Metalloproteinases; Myocardium; Physical Conditioning, Animal; Rats; Rats, Inbred BN; Rats, Inbred F344; Tissue Inhibitor of Metalloproteinase-1; Transforming Growth Factor beta; Ventricular Remodeling
PubMed: 21148111
DOI: 10.1096/fj.10-172924 -
Relationship between matrix metalloproteinases and the occurrence and development of ovarian cancer.Brazilian Journal of Medical and... May 2017Ovarian cancer is one of the most malignant genital cancers, with a high mortality rate. Many researchers have suggested that matrix metalloproteinases (MMPs) have... (Review)
Review
Ovarian cancer is one of the most malignant genital cancers, with a high mortality rate. Many researchers have suggested that matrix metalloproteinases (MMPs) have remarkably high expression in ovarian cancer tissues. MMPs are considered to be related to the occurrence, development, invasion and metastasis of ovarian cancer. Moreover, some studies have discovered that the unbalance between MMPs and tissue inhibitor of metalloproteinases (TIMPs) are associated with the malignant phenotype of tumors. This review summarizes the latest research progress of MMPs in ovarian cancer. The investigation of MMP mechanism in ovarian cancer will facilitate the development of effective anti-tumor drugs, and thereby improve the survival rate of patients with ovarian cancer.
Topics: Biomarkers, Tumor; Female; Gene Expression; Humans; Matrix Metalloproteinase Inhibitors; Matrix Metalloproteinases; Ovarian Neoplasms; Tissue Inhibitor of Metalloproteinases
PubMed: 28538838
DOI: 10.1590/1414-431X20176104 -
Journal of Cancer Research and... 2016The family of human matrix metalloproteinases (MMPs) comprises several tightly regulated classes of proteases. These enzymes and their specific inhibitors play important... (Review)
Review
The family of human matrix metalloproteinases (MMPs) comprises several tightly regulated classes of proteases. These enzymes and their specific inhibitors play important roles in tumor progression and the metastatic process by facilitating extracellular matrix (ECM) degradation. As scientific understanding of the MMPs has advanced, therapeutic strategies focusing on blocking these enzymes by MMP inhibitors (MMPIs) have rapidly developed. This paper reviews MMPs in detail. Their perspectives in therapeutic intervention in cancer are also mentioned.
Topics: Carcinogenesis; Extracellular Matrix; Humans; Matrix Metalloproteinase Inhibitors; Matrix Metalloproteinases; Neoplasms
PubMed: 27072206
DOI: 10.4103/0973-1482.157337 -
Biology of Sex Differences May 2023Alzheimer's disease (AD) can be characterised in vivo by biomarkers reflecting amyloid-β (Aβ) and tau pathology. However, there is a need for biomarkers reflecting...
INTRODUCTION
Alzheimer's disease (AD) can be characterised in vivo by biomarkers reflecting amyloid-β (Aβ) and tau pathology. However, there is a need for biomarkers reflecting additional pathological pathways. Matrix metalloproteinases (MMPs) have recently been highlighted as candidate biomarkers for sex-specific mechanisms and progression in AD.
METHODS
In this cross-sectional study, we investigated nine MMPs and four tissue inhibitors of metalloproteinases (TIMPs) in the cerebrospinal fluid of 256 memory clinic patients with mild cognitive impairment or dementia due to AD and 100 cognitively unimpaired age-matched controls. We studied group differences in MMP/TIMP levels and examined the associations with established markers of Aβ and tau pathology as well as disease progression. Further, we studied sex-specific interactions.
RESULTS
MMP-10 and TIMP-2 levels differed significantly between the memory clinic patients and the cognitively unimpaired controls. Furthermore, MMP- and TIMP-levels were generally strongly associated with tau biomarkers, whereas only MMP-3 and TIMP-4 were associated with Aβ biomarkers; these associations were sex-specific. In terms of progression, we found a trend towards higher MMP-10 at baseline predicting more cognitive and functional decline over time exclusively in women.
CONCLUSION
Our results support the use of MMPs/TIMPs as markers of sex differences and progression in AD. Our findings show sex-specific effects of MMP-3 and TIMP-4 on amyloid pathology. Further, this study highlights that the sex-specific effects of MMP-10 on cognitive and functional decline should be studied further if MMP-10 is to be used as a prognostic biomarker for AD.
Topics: Humans; Female; Male; Alzheimer Disease; Matrix Metalloproteinase 10; Matrix Metalloproteinase 3; Cross-Sectional Studies
PubMed: 37221606
DOI: 10.1186/s13293-023-00514-x -
Biomedicine & Pharmacotherapy =... Jan 2023Cluster of differentiation 147 (CD147) or extracellular matrix metalloproteinase inducer (EMMPRIN) is a transmembrane glycoprotein that induces the synthesis of matrix... (Review)
Review
Cluster of differentiation 147 (CD147) or extracellular matrix metalloproteinase inducer (EMMPRIN) is a transmembrane glycoprotein that induces the synthesis of matrix metalloproteinases (MMPs). MMPs, as zinc-dependent proteases and versatile enzymes, play critical roles in the degradation of the extracellular matrix (ECM) components, cleaving of the receptors of cellular surfaces, signaling molecules, and other precursor proteins, which may lead to attenuation or activation of such targets. CD147 and MMPs play essential roles in physiological and pathological conditions and any disorder in the expression, synthesis, or function of CD147 and MMPs may be associated with various types of disease. In this review, we have focused on the roles of CD147 and MMPs in some major physiological and pathological processes.
Topics: Matrix Metalloproteinases; Basigin
PubMed: 36370522
DOI: 10.1016/j.biopha.2022.113983 -
Experimental Biology and Medicine... Dec 2016The wide array of proteases, including matrix metalloproteinases, produced in response to many pathogenic insults, confers a unique proteolytic signature which is often...
The wide array of proteases, including matrix metalloproteinases, produced in response to many pathogenic insults, confers a unique proteolytic signature which is often disease specific and provides a potential therapeutic target for drug delivery. Here we propose the use of collagen-based nanoenhanced matrix metalloproteinase-responsive delivery vehicles that display matrix metalloproteinase-specific degradation in diverse in vitro models of proteolysis. We demonstrate that collagen particles comprised of protease substrates (primarily collagen) can be made of uniform size and loaded efficiently with assorted cargo including fluorescently labeled mesoporous silica, magnetic nanoparticles, proteins and antioxidants. We also demonstrate that pathologic concentrations of proteases produced in situ or in vitro display protease-specific cargo release. Additionally, we show that the collagen-based particles display bright fluorescence when loaded with a fluorophore, and have the potential to be used as vehicles for targeted delivery of drugs or imaging agents to regions of high proteolytic activity.
Topics: Blotting, Western; Cell Line; Collagen; Drug Delivery Systems; Fibroblasts; Fluorescence; Humans; In Vitro Techniques; Matrix Metalloproteinases; Metal Nanoparticles; Proteolysis
PubMed: 27474175
DOI: 10.1177/1535370216662534 -
Arthritis Research 2002The role of matrix metalloproteinases in the degradative events invoked in the cartilage and bone of arthritic joints has long been appreciated and attempts at the... (Review)
Review
The role of matrix metalloproteinases in the degradative events invoked in the cartilage and bone of arthritic joints has long been appreciated and attempts at the development of proteinase inhibitors as potential therapeutic agents have been made. However, the spectrum of these enzymes orchestrating connective tissue turnover and general biology is much larger than anticipated. Biochemical studies of the individual members of the matrix metalloproteinase family are now underway, ultimately leading to a more detailed understanding of the function of their domain structures and to defining their specific role in cellular systems and the way that they are regulated. Coupled with a more comprehensive and detailed study of proteinase expression in different cells of joint tissues during the progress of arthritic diseases, it will be possible for the future development and application of highly specific proteinase inhibitors to be directed at specific key cellular events.
Topics: Arthritis, Rheumatoid; Humans; Matrix Metalloproteinases; Protein Structure, Tertiary
PubMed: 12110122
DOI: 10.1186/ar572 -
Biomolecules Jan 2023Matrix metalloproteinases (MMPs) are a large family of zinc-dependent proteolytic enzymes associated with extracellular matrix protein turnover and tissue degradation.... (Review)
Review
Matrix metalloproteinases (MMPs) are a large family of zinc-dependent proteolytic enzymes associated with extracellular matrix protein turnover and tissue degradation. They participate to many different physiological reactions but are also hyperactivated in several diseases. Various literature studies have documented that MMPs play a role in the modulation of neuropathic and nociceptive pain. The heterogeneity of clinical and pre-clinical data is an important issue in this experimental context. Despite the presence of a good number of studies on MMP inhibitors, these drugs showed scarce efficacy and relevant side effects. In the present manuscript, we reviewed studies in the literature that define a possible role of MMPs in pain and the effects of their modulation.
Topics: Humans; Matrix Metalloproteinase Inhibitors; Matrix Metalloproteinases; Pain
PubMed: 36830637
DOI: 10.3390/biom13020268 -
The European Respiratory Journal Nov 2002The purpose of this study was to examine the role of interstitial collagenases, members of the family of matrix metalloproteinases, in the development of pulmonary...
The purpose of this study was to examine the role of interstitial collagenases, members of the family of matrix metalloproteinases, in the development of pulmonary fibrosis. The activity, levels and molecular forms of collagenases (matrix metalloproteinases (MMP)-1, -8 and -13), gelatinase B (MM P-9) and its main endogenous inhibitor, tissue inhibitor of metalloproteinase-1 (TIMP-1) were assessed in bronchoalveolar lavage fluid (BALF) from patients with idiopathic pulmonary fibrosis (IPF) and sarcoidosis patients with varying degrees of pulmonary parenchymal involvement. Collagenase activity was elevated in IPF and group 3 sarcoidosis patients. A positive correlation between BALF collagenase activity and MMP-8 levels was also observed. Western immunoblotting revealed the presence of two isoforms of MMP-8 in patient samples; an 80 kD form representing latent enzyme from polymorphonuclear neutrophils and a 55 kD form representing the fibroblast-type proform. MMP-9 levels were also elevated in both IPF and group 3 sarcoidosis patients, while TIMP-1 levels remained normal, indicating a shift in the balance between the enzyme and inhibitor, favouring MMP-9. Matrix metalloproteinase-8 is the major contributor to the bronchoalveolar lavage fluid collagenase activity in the airways of patients with idiopathic pulmonary fibrosis and sarcoidosis and may initiate collagen destruction and remodelling leading to the development of pulmonary fibrosis.
Topics: Aged; Blotting, Western; Bronchoalveolar Lavage Fluid; Collagenases; Female; Humans; Male; Matrix Metalloproteinase 8; Matrix Metalloproteinase 9; Matrix Metalloproteinases; Middle Aged; Pulmonary Fibrosis; Sarcoidosis, Pulmonary; Tissue Inhibitor of Metalloproteinase-1
PubMed: 12449177
DOI: 10.1183/09031936.02.00022302 -
Critical Reviews in Eukaryotic Gene... 2008Matrix metalloproteinases (MMPs) play crucial roles in a variety of normal (e.g., blood vessel formation, bone development) and pathophysiological (e.g., wound healing,... (Review)
Review
Matrix metalloproteinases (MMPs) play crucial roles in a variety of normal (e.g., blood vessel formation, bone development) and pathophysiological (e.g., wound healing, cancer) processes. This is not only due to their ability to degrade the surrounding extracellular matrix (ECM), but also because MMPs function to reveal cryptic matrix binding sites, release matrix-bound growth factors inherent to these processes, and activate a variety of cell surface molecules. The process of blood vessel formation, in particular, is regulated by what is widely classified as the angiogenic switch: a mixture of both pro- and antiangiogenic factors that function to counteract each other unless the stimuli from one side exceeds the other to disrupt the quiescent state. Although it was initially thought that MMPs were strictly proangiogenic, new functions for this proteolytic family, such as mediating vascular regression and generating matrix fragments with antiangiogenic capacities, have been discovered in the last decade. These findings cast MMPs as multifaceted pro- and antiangiogenic effectors. The purpose of this review is to introduce the reader to the general structure and characterization of the MMP family and to discuss the temporal and spatial regulation of their gene expression and enzymatic activity in the following crucial steps associated with angiogenesis: degradation of the vascular basement membrane, proliferation and invasion of endothelial cells within the subjacent ECM, organization into immature tubules, maturation of these nascent vessels, and the pruning and regression of the vascular network.
Topics: Angiogenesis Inhibitors; Animals; Capillaries; Cell Proliferation; Endothelial Cells; Extracellular Matrix; Humans; Matrix Metalloproteinase Inhibitors; Matrix Metalloproteinases; Morphogenesis
PubMed: 18540825
DOI: 10.1615/critreveukargeneexpr.v18.i3.30