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Frontiers in Immunology 2022Inflammatory bowel disease (IBD) has become globally intractable. MMPs play a key role in many inflammatory diseases. However, little is known about the role of MMPs in...
Inflammatory bowel disease (IBD) has become globally intractable. MMPs play a key role in many inflammatory diseases. However, little is known about the role of MMPs in IBD. In this study, IBD expression profiles were screened from public Gene Expression Omnibus datasets. Functional enrichment analysis revealed that IBD-related specific functions were associated with immune pathways. Five MMPS-related disease markers, namely MMP-9, CD160, PTGDS, SLC26A8, and TLR5, were selected by machine learning and the correlation between each marker and immune cells was evaluated. We then induced colitis in C57 mice using sodium dextran sulfate and validated model construction through HE staining of the mouse colon. WB and immunofluorescence experiments confirmed that the expression levels of MMP-9, PTGDS, SLC26A8, and CD160 in colitis were significantly increased, whereas that of TLR5 were decreased. Flow cytometry analysis revealed that MMPs regulate intestinal inflammation and immunity mainly through CD8 in colitis. Our findings reveal that MMPs play a crucial role in the pathogenesis of IBD and are related to the infiltration of immune cells, suggesting that MMPs may promote the development of IBD by activating immune infiltration and the immune response. This study provides insights for further studies on the occurrence and development of IBD.
Topics: Animals; Mice; Matrix Metalloproteinase 9; Toll-Like Receptor 5; Inflammatory Bowel Diseases; Colitis; Matrix Metalloproteinases
PubMed: 36733384
DOI: 10.3389/fimmu.2022.1067950 -
Journal of Translational Medicine Mar 2023Head and Neck Squamous Cell Carcinoma is a malignant tumor with high morbidity and mortality. The MMP family plays an important role in tumor invasion and metastasis....
BACKGROUND
Head and Neck Squamous Cell Carcinoma is a malignant tumor with high morbidity and mortality. The MMP family plays an important role in tumor invasion and metastasis. However, the mechanistic value of the MMP family as a therapeutic target and prognostic biomarker in HNSC has not been fully elucidated.
METHODS
Oncomine, UALCAN, GEPIA, cBioportal, GeneMANIA, STRING, DAVID6.8, TRRUST, TIMER and Linkedomics were used for analysis.
RESULTS
The mRNA expression levels of MMP1, MMP3, ILF3, MMP7, MMP9, MMP10, MMP11, MMP12, MMP13 and MMP16 were higher in HNSC than those in normal tissues, while the mRNA expression level of MMP15 was reduced. The relative expression levels of MMP1 and MMP14 were the highest in HNSC tissues. A significant correlation was found between the expression of MMP3, MMP11, MMP25 and the pathological stage of HNSC patients. There was no significant associations between all the MMP family members expression levels and DFS. Increased mRNA levels of MMP1, MMP8 and MMP25 were significantly associated with OS. In addition, we investigated the genetic changes of the MMP family in HNSC and found that all the MMP family members had genetic changes, most of which were amplification and depth loss. In the analysis of neighbor gene network and protein interaction, we found that the MMP family interacted with 25 neighboring genes, except for ILF3, MMP19, MMP20, MMP21, MMP23B, MMP27 and MMP28, other MMP proteins interacted with each other. Functional enrichment analysis showed that the MMP family could be present in the extracellular matrix, regulate peptidase activity, and participate in the catabolism of collagen. Meanwhile, we identified the transcription factor targets and kinase targets of the MMP family and found that ATM and ATR were the two most common kinase targets in the MMP family. We also found a significant correlation between the MMP family expression and immune cell infiltration. Cox proportional risk model analysis showed that macrophages, MMP14, MMP16, and MMP19 were significantly associated with clinical outcomes in HNSC patients.
CONCLUSION
The MMP family might serve as therapeutic target and prognostic biomarker in HNSC.
Topics: Humans; Biomarkers, Tumor; Head and Neck Neoplasms; Matrix Metalloproteinase 1; Matrix Metalloproteinase 11; Matrix Metalloproteinase 14; Matrix Metalloproteinase 16; Matrix Metalloproteinase 3; Prognosis; Squamous Cell Carcinoma of Head and Neck; Tumor Microenvironment; Matrix Metalloproteinases
PubMed: 36941602
DOI: 10.1186/s12967-023-04052-3 -
International Journal of Molecular... Jan 2019MT4-MMP (or MMP17) belongs to the Membrane-Type Matrix Metalloproteinase (MT-MMP) family. This family of proteases contributes to extracellular matrix remodeling during... (Review)
Review
MT4-MMP (or MMP17) belongs to the Membrane-Type Matrix Metalloproteinase (MT-MMP) family. This family of proteases contributes to extracellular matrix remodeling during several physiological processes, including embryogenesis, organogenesis, tissue regeneration, angiogenesis, wound healing, and inflammation. MT4-MMP (MMP17) presents unique characteristics compared to other members of the family in terms of sequence homology, substrate specificity, and internalization mode, suggesting distinct physiological and pathological functions. While the physiological functions of MT4-MMP are poorly understood, it has been involved in different pathological processes such as arthritis, cardiovascular disease, and cancer progression. The transcript has been detected in a large diversity of cancers. The contribution of MT4-MMP to tumor development has been further investigated in gastric cancer, colon cancer, head and neck cancer, and more deeply in breast cancer. Given its contribution to different pathologies, particularly cancers, MT4-MMP represents an interesting therapeutic target. In this review, we examine its biological and structural properties, and we propose an overview of its physiological and pathological functions.
Topics: Animals; Disease; Glycosylphosphatidylinositols; Humans; Matrix Metalloproteinase Inhibitors; Matrix Metalloproteinases, Membrane-Associated; Models, Biological
PubMed: 30654475
DOI: 10.3390/ijms20020354 -
The Journal of Thoracic and... Jan 2007The altered expression of matrix metalloproteinases and their inhibitors influences the formation of atherosclerotic abdominal aortic aneurysms. Their association with...
OBJECTIVES
The altered expression of matrix metalloproteinases and their inhibitors influences the formation of atherosclerotic abdominal aortic aneurysms. Their association with thoracic aneurysms is less clear. This study describes the expression of metalloproteinases and their inhibitors in atherosclerotic and nonatherosclerotic thoracic aneurysms, and compares these with age-matched controls.
METHODS
Matrix metalloproteinase-2 and 9 activity were measured by antibody capture, and tissue inhibitor-1 and 2 levels were measured by enzyme-linked immunosorbent assay in 24 patients with atherosclerotic aneurysms and in 63 patients with nonatherosclerotic aneurysms. Gene expression was assessed with reverse transcriptase polymerase chain reaction. The results were compared with 17 controls.
RESULTS
Data are in nanograms per milligram of protein. Matrix metalloproteinase-2 activity was greater in controls than in the atherosclerotic and nonatherosclerotic groups (80 +/- 67 vs 49 +/- 50 and 35 +/- 44, P = .002). Matrix metalloproteinase-9 activity was greater in the atherosclerotic group than in the nonatherosclerotic group and controls (11.7 +/- 15.7 vs 2.5 +/- 2.2 and 1.7 +/- 1.9, P = .001). Tissue inhibitor-1 and 2 levels were greater in controls than in either aneurysm group (tissue inhibitor of metalloproteinase-1: 376 +/- 192 vs 234 +/- 233 and 174 +/- 148, P = .003; tissue inhibitor of metalloproteinase-2: 143 +/- 74 vs 14 +/- 13 and 27 +/- 43, P < .001). Atherosclerotic aneurysms expressed more matrix metalloproteinase mRNA than controls.
CONCLUSIONS
The metalloproteinase/tissue inhibitor phenotype of atherosclerotic thoracic aneurysms is similar to that of abdominal aneurysms. The diminished expression of metalloproteinases and tissue inhibitors in nonatherosclerotic thoracic aneurysms relative to aged controls may represent a loss of smooth muscle cells.
Topics: Aged; Aortic Aneurysm, Thoracic; Atherosclerosis; Female; Gene Expression; Humans; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Matrix Metalloproteinases; Middle Aged; Tissue Inhibitor of Metalloproteinase-1; Tissue Inhibitor of Metalloproteinase-2; Tissue Inhibitor of Metalloproteinases
PubMed: 17198804
DOI: 10.1016/j.jtcvs.2006.07.036 -
Molecular Neurobiology Nov 2016Traumatic brain injury (TBI) is a major cause of mortality and morbidity worldwide. Studies revealed that the pathogenesis of TBI involves upregulation of MMPs. MMPs... (Review)
Review
Traumatic brain injury (TBI) is a major cause of mortality and morbidity worldwide. Studies revealed that the pathogenesis of TBI involves upregulation of MMPs. MMPs form a large family of closely related zinc-dependent endopeptidases, which are primarily responsible for the dynamic remodulation of the extracellular matrix (ECM). Thus, they are involved in several normal physiological processes like growth, development, and wound healing. During pathophysiological conditions, MMPs proteolytically degrade various components of ECM and tight junction (TJ) proteins of BBB and cause BBB disruption. Impairment of BBB causes leakiness of the blood from circulation to brain parenchyma that leads to microhemorrhage and edema. Further, MMPs dysregulate various normal physiological processes like angiogenesis and neurogenesis, and also they participate in the inflammatory and apoptotic cascades by inducing or regulating the specific mediators and their receptors. In this review, we explore the roles of MMPs in various physiological/pathophysiological processes associated with neurological complications, with special emphasis on TBI.
Topics: Animals; Blood-Brain Barrier; Brain Injuries, Traumatic; Humans; Matrix Metalloproteinase Inhibitors; Matrix Metalloproteinases; Molecular Targeted Therapy
PubMed: 26541883
DOI: 10.1007/s12035-015-9520-8 -
Advances in Clinical and Experimental... 2016Matrix metalloproteinases (MMPs) belong to a family of structurally related zinc-dependent proteolytic enzymes that are known to play a key role in the catabolic... (Review)
Review
Matrix metalloproteinases (MMPs) belong to a family of structurally related zinc-dependent proteolytic enzymes that are known to play a key role in the catabolic turnover of extracellular matrix (ECM) components. Research studies to date have indicated that MMPs regulate the activity of several non-ECM bioactive substrates, including growth factors, cytokines, chemokines and cell receptors, which determine the tissue microenvironment. Disruption of the balance between the concentration of active matalloproteinases and their inhibitors (TIMPs) may lead to pathological changes associated with uncontrolled ECM turnover, tissue remodeling, inflammatory response, cell growth and migration. This brief review presents some information on MMPs' role in inflammatory, metabolic and cancer abnormalities related to the salivary glands, as well as MMP-related aspects that lead to the formation of human dentinal caries lesions. In oral diseases, the most relevant biological fluid commonly used for diagnosing periodontal diseases is saliva. In diseased patients with significantly higher levels of MMPs in their saliva than healthy people, most extracellular matrix components undergo digestion to lower molecular weight forms. Conventional treatment successfully reduces the levels of MMPs inhibits the progressive breakdown of gingival and periodontal ligament collagens. Beside inflammatory abnormalities like Sjögren's syndrome (SS), a large group of disorders is comprised of cancers, most of them involving the parotid gland.
Topics: Animals; Dental Caries; Humans; Matrix Metalloproteinase Inhibitors; Matrix Metalloproteinases; Protein Conformation; Saliva; Salivary Gland Diseases; Salivary Glands; Structure-Activity Relationship
PubMed: 27627574
DOI: 10.17219/acem/30428 -
BioMed Research International 2022To investigate the risk of cardiovascular and neurodegenerative diseases induced by matrix metalloproteinases (MMPs) by meta-analysis. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To investigate the risk of cardiovascular and neurodegenerative diseases induced by matrix metalloproteinases (MMPs) by meta-analysis.
METHODS
Relevant literature was searched from Wanfang Medical Center, CNQI, VIP, PubMed, and other domestic and foreign literature databases for the research direction, and the risk of cardiovascular and neurodegenerative diseases induced by MMPs was meta-analyzed using the fixed-effect model and random-effect model.
RESULTS
MMP-1 and MMP-9 were risk factors for cardiovascular diseases by fixed and random-effect model analysis, respectively, while MMP-2 and MMP-9 were risk factors for increased neurodegenerative diseases by random-effect model analysis.
CONCLUSION
MMP-1 and MMP-9 are risk factors for cardiovascular diseases, and MMP-2 and MMP-9 are major factors for increased risk of neurodegenerative diseases. MMP-1, MMP-2, and MMP-9 can be used as new targets for clinical diagnosis, treatment, and research of subsequent cardiovascular and neurodegenerative diseases.
Topics: Humans; Matrix Metalloproteinase 9; Matrix Metalloproteinase 2; Neurodegenerative Diseases; Matrix Metalloproteinase 1; Cardiovascular Diseases; Matrix Metalloproteinases
PubMed: 36277880
DOI: 10.1155/2022/3360316 -
Medicina (Kaunas, Lithuania) May 2019Cardiac remodeling in pregnancy and postpartum is poorly understood. The aim of this study was to evaluate changes in cardiac fibrosis (pericardial, perivascular, and...
Cardiac remodeling in pregnancy and postpartum is poorly understood. The aim of this study was to evaluate changes in cardiac fibrosis (pericardial, perivascular, and interstitial), as well as the expression of matrix metalloproteinases (MMP-1, MMP-2, and MMP-9) and their inhibitors (Tissue inhibitors of metalloproteinases, TIMP-1 and TIMP-4) during late pregnancy and postpartum in rat left ventricle. Female Sprague-Dawley rats were used for this study. Rats were divided three groups: non-pregnant, late pregnancy, and postpartum. The heart was weighed and cardiac fibrosis was studied by conventional histological procedures. The expression and transcript level of target proteins were evaluated using immunoblot techniques and quantitative PCR. The experiments showed an increase of perivascular, pericardial, and interstitial fibrosis in heart during pregnancy and its reversion in postpartum. Moreover, in late pregnancy, MMP-1, MMP-2, and MMP-9 metalloproteinases were downregulated and TIMP-1 and TIMP-4 were upregulated in left ventricle. Our data suggest that the metalloproteinases system is involved in the cardiac extracellular matrix remodeling during pregnancy and its reversion in postpartum, this improves the knowledge of the adaptive cardiac remodeling in response to a blood volume overload present during pregnancy.
Topics: Animals; Disease Models, Animal; Female; Fibrosis; Heart Ventricles; Matrix Metalloproteinase 1; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Matrix Metalloproteinases; Postpartum Period; Pregnancy; Rats; Rats, Sprague-Dawley; Tissue Inhibitor of Metalloproteinase-1; Tissue Inhibitor of Metalloproteinase-2
PubMed: 31126142
DOI: 10.3390/medicina55050199 -
Molecular Pathology : MP Jun 1999The process of metastasis is complex, involving many interrelated stages, including proteolysis. Proteolysis occurs in both normal and pathological processes and...
BACKGROUND
The process of metastasis is complex, involving many interrelated stages, including proteolysis. Proteolysis occurs in both normal and pathological processes and involves the breakdown of the extracellular matrix and/or basement membrane by proteolytic enzymes. Normally, proteolysis is tightly controlled by specific endogenous proteinase inhibitors. However, in certain disease processes, including cancer, controlled but abnormal proteolysis seems to occur. Proteinases involved in tumour invasion and metastasis include the matrix metalloproteinases (MMPs) and the serine proteinases.
AIMS
To gain a greater understanding of the proteolytic process occurring in colorectal cancer and to determine which, if any, proteinases are upregulated.
METHODS
The synthesis of proteinases and their inhibitors was compared in paired tumour and normal tissue samples from patients with colorectal cancer (n = 24). Substrate zymography was used to determine the synthesis of MMPs (MMP-2, MMP-9, and MMP-3) and the plasminogen activators (urokinase and tissue-type plasminogen activators); enzyme linked immunosorbent assays (ELISAs) were used to determine the concentrations of MMP-1 and tissue inhibitor of metalloproteinase 1 (TIMP-1); and the technique of quenched fluorescence substrate hydrolysis was performed to determine the total MMP activity of each sample.
RESULTS
In general, both proteinase and inhibitor expression was greater in the tumour tissue when compared with the corresponding normal colorectal tissue. The amount of active MMPs was greater in the tumour tissue.
CONCLUSIONS
The increased extracellular proteinase concentrations and activity may encourage tumour invasion and metastasis. This study points to MMP-9 as being of potential major importance in the development of this form of cancer.
Topics: Colorectal Neoplasms; Enzyme-Linked Immunosorbent Assay; Humans; Matrix Metalloproteinase 2; Matrix Metalloproteinase 3; Matrix Metalloproteinase 9; Matrix Metalloproteinases; Plasminogen Activators; Tissue Inhibitor of Metalloproteinase-1
PubMed: 10621835
DOI: 10.1136/mp.52.3.140 -
Journal of Cellular Biochemistry Dec 2009In response to injury, epithelial cells migrate across the denuded tissue to rapidly close the wound and restore barrier, thereby preventing the entry of pathogens and... (Review)
Review
In response to injury, epithelial cells migrate across the denuded tissue to rapidly close the wound and restore barrier, thereby preventing the entry of pathogens and leakage of fluids. Efficient, proper migration requires a range of processes, acting both inside and out of the cell. Among the extracellular responses is the expression of various matrix metalloproteinases (MMPs). Though long thought to ease cell migration simply by breaking down matrix barriers, findings from various models demonstrate that MMPs facilitate (and sometimes repress) cell movement by other means, such as affecting the state of cell-matrix interactions or proliferation. In this Prospect, we review some key data indicting how specific MMPs function via their activity as proteinases to control closure of epithelial wounds.
Topics: Animals; Cell Movement; Epithelial Cells; Humans; Matrix Metalloproteinase 14; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Matrix Metalloproteinases; Wound Healing
PubMed: 19798678
DOI: 10.1002/jcb.22363