جستجوی مقالات مرتبط با کلیدواژه "matrix metalloproteinases" در نشریات گروه "پزشکی"

Matrix Metalloproteinases (MMPs) are inflammatory mediators involved in bacterial infection and other pathological conditions. Inflammation can damage all parts of the brain, particularly sensitive areas such as the hippocampus. Chronic stress can make the brain more susceptible to infection and inflammation. This study aimed to investigate the effects of stress on the activity of MMP2 and MMP9 in the hippocampus of male Wistar rats following the administration of Brucella Melitensis (BM) vaccine.

The non-stressed group received a Brucella Melitensis vaccine strain via intracebroventicular (i.c.v) and intraperitoneal (i.p) routes. The animals were subjected to heterogeneous sequential stress for nine days and/or received the same volume of Brucella Melitensis vaccine (BMV). The activity of MMP-2 and MMP-9 was measured by Gelatin Zymography.

The results showed that stress increased the activity of MMP9 in both the control group and the BMV, i.p., injected animals. However, stress did not affect the activity of MMP2 in either the control or the BM, i.p., inoculated conditions. Stress also increased the activity of MMP9 following i.c.v. injection of BM, without a concomitant change in the activity of MMP2 in the hippocampus.

The study suggests that vaccination in stressed conditions could activate MMPs, which are essential players in inflammatory processes, in brain of immunized animals. Since the Brucella melitensis vaccine is used for the prophylaxis of brucellosis in small ruminants, these findings have important implications for understanding the effects of stress on the immune response to vaccination and inflammation in the brain.

One prevalent malignant tumor in the digestive system is gastric cancer (GC). Cortactin is an intracellular cytoskeleton protein and exerts the crucial function in GC development. However, the roles and mechanisms of cortactin in the invasion and metastasis of GC need further exploration.

Cortactin expression in GC tissues and cells via western blot and quantitative reverse transcription PCR. Cell migration and invasion were detected by the Transwell assays. Immunofluorescence staining and extracellular matrix (ECM) degradation assays verified the ability to invadopodium formation and ECM degradation.We then used gelatin zymography to identify the relationship between cortactin and matrix metalloproteinases (MMPs). The xenograft tumor model proved that cortactin can accelerate tumor growth and intraperitoneal metastasis in mice.

We found that cortactin is overexpressed in GC. cortactin overexpression facilitated cell migration and invasion, whereas cortactin silencing exerted the opposite function. cortactin can facilitate invadopodium formation and ECM degradation in GC cells. Cortactin can positively regulate matrix metalloproteinase 2 (MMP2) and matrix metalloproteinase 9 (MMP9) levels. Furthermore, Cortactin accelerate GC progression in vivo.

In short, this study confirmed that cortactin enhanced invadopodium formation to accelerate GC development through upregulating MMP2 and MMP9.

 Based on the critical role of MT4-MMP and MT6-MMP in carcinogenesis, we focused on MT4-MMP and MT6-MMP circulating levels in patients with thyroid nodules.

 Plasma samples were collected from three groups, including papillary thyroid cancer (PTC; n=30), multinodular goiter (MNG; n=30), and healthy subjects (n=22). Enzyme-linked immunosorbent assay (ELISA) was used to obtain the concentration of MT4-MMP and MT6-MMP in the three groups.

 Analysis of data demonstrated increased levels of MT4-MMP (PTC: 4.90±1.35, MNG: 4.89±1.37, and healthy: 3.13±1.42) and MT6-MMP (PTC: 8.29±2.50, MNG: 7.34±2.09, and healthy:5.01±2.13) in thyroid nodules by comparison with healthy subjects (P<0.05). There were no significant differences in the levels of the two MT-MMPs between PTC and MNG (P>0.05). Increased plasma levels of MT4-MMP (odds ratio=2.48; 95% CI: 1.46–4.19; P=0.001) or MT6-MMP (odds ratio=1.81; 95% CI: 1.29–2.53; P=0.001) were associated with increased risk of PTC tumorigenesis. Interestingly, a strong positive association was observed between MT4-MMP and MT6-MMP in the three groups (PTC: r=0.766**, P=0.000; MNG: r=0.856**, P=0.000; healthy r=0.947**, P=0.000). Areas under the ROC curve for MT4-MMP and MT6-MMP were 0.82 and 0.96, respectively. At the cutoff value>4.7 (ng/mL), MT4-MMP and MT6-MMP showed a sensitivity of 63.3% and 90.0%, respectively, with 100% specificity.

 Our work has led us to imply that the higher levels of MT4-MMP and MT6-MMP are closely linked with both PTC and MNG tumorigenesis. They may probably promote the development of thyroid lesions; however, more research is needed to further clarify the current findings.

Cutis laxa (CL) is a connective tissue disease that is either inherited or acquired. It is characterized by redundant, pendulous, and inelastic skin. Loss of elasticity is a pathological feature of some degenerative and inflammatory diseases. Matrix metalloproteinases (MMPs) can cleave elastin fibers by damaging the microfibrils and the elastin core, resulting in the loss of elasticity. In this study, we report eight patients with different types of cutis laxa along with the quantitative measurement of serum levels of MMP-2 and MMP-9. The cutis laxa patients showed various clinical and histopathological findings, indicating the heterogeneity of this rare skin connective tissue disease. The serum level of MMP-2 and MMP-9 were elevated in these patients. Increased MMP-2 and MMP-9 might be associated with cutis laxa. However, our findings need to be validated in larger clinical settings.

It is believed that preformed antibodies are responsible for blood transfusion reactions and transplant rejections. In order to remove a tumor, the tissue must be rejected. On the basis of transfusion reaction and transplantation immunology, we hypothesized that allogeneic serum can inhibit tumor growth when injected intra-tumor. Initially, an in vitro cytotoxicity test was conducted using the C57BL/6 serum (intact or decomplemented) in combination with the BALB/c-originating CT26 cell line.  The CT26 cell line was used to establish a mouse model of colon cancer. When the tumor was palpable, C57BL/6 serum was injected intra-tumor. In addition to tumor size, hypoxia, metastatic capacity, angiogenesis, and metabolic and inflammatory status, we evaluated matrix metalloproteinase-2 (MMP)-2 and 9, vascular endothelial growth factor (VEGF)-A, Cluster of Designation (CD) 31, CD38 and interleukine (IL)-10. An in vitro experiment showed that heat-inactivated C57BL/6 serum had significantly lower cytotoxic effects on BALB/c-derived CT26 cells than intact C57BL/6 serum or BALB/c serum. In vivo experiments revealed that tumor size, HIF-1α, MMP-2, and MMP-9 levels were significantly lower in the experimental group than in the control group. In contrast to control animals, allogeneic serum treatment led to marked reductions in CD31, VEGF-1, CD38, and IL-10 levels. A new approach to serum or plasma therapy and allogeneic vaccines for cancer is intra-tumor injection of allogeneic serum. In light of the ease and availability of allogeneic immunotherapies, allogeneic serum and plasma therapy could potentially be used as an alternative monotherapy or in combination with other therapies.

Glioblastoma is an aggressive human brain malignancy with poorly understood pathogenesis. Voltage-gated potassium (Kv) channels and Matrix Metalloproteinases (MMPs) are highly expressed in malignant tumors and involved in the progression and metastasis of glioblastoma. This study aimed to determine whether a voltage-dependent potassium channel blocker could modulate astrocytes as a cell involved in the immunopathogenesis of glioblastoma. 

The cytotoxic effect of 4-Aminopyridine (4-AP) at different doses in the cell model of glioblastoma was measured by MTT assay. The ELISA technique and gelatin zymography were used to assess cytokine levels and MMP-9 after 4-AP treatment. 

Cytotoxicity analysis data indicated that cell viability reduced by increasing 4-AP level and cell growth decreased gradually by removing 4-AP from the cell medium. 4-AP inhibits the secretion of IL-6 and IL-1 (P<0.05). MMP9 activity significantly inhibits with increased 4-AP dose, compared to non-treated cells.

The reduction of cell viability, IL-6 secretion, and MMP-9 activity in an in vitro model of glioblastoma might be assumed 4-AP as an agent for chemoprevention of cancer.

Coronary artery disease (CAD) is the most common type of cardiovascular disease. Increasing the expression and activity of matrix metalloproteinases (MMPs) facilitates vascular remodeling and cardiovascular complications. Curcumin (the active ingredient of turmeric) is a potent natural anti-inflammatory agent, with cardiovascular protective effects. The present study was a clinical trial for investigating the effects of curcumin on activity and gene expression of MMP-2 and MMP-9 in patients with CAD.

In this study, 70 patients with CAD (with 40%-50% stenosis) were randomly divided into two groups of curcumin (80 mg nanomicelle per day) and placebo. The intervention lasted 3 months. The activity levels of MMP-2 and MMP-9 in serum samples of patients were measured using gelatin zymography assay before and after the intervention. MMP-2 and MMP9 gene expression in peripheral blood mononuclear cells (PBMCs) was also analyzed using realtime polymerase chain reaction (PCR). Statistical significance was set at P < 0.0500.

After 3 months of medication, the expression of MMP-9 produced by PBMCs significantly decreased in the curcumin group (0.811 ± 0.25) in comparison with the placebo group (2.23 ± 0.94) (P < 0.0001). Furthermore, the zymographic analysis showed that the administration of curcumin significantly inhibited the activity levels of MMP-2 (12469.7 ± 5308.64 pixels) and MMP-9 (14007.2 ± 5371.67 pixels) in comparison with that in patients receiving placebo (MMP-2: 17613.8 ± 5250.68 pixels; MMP-9: 20010.1 ± 3259.37 pixels) (P < 0.0500).

Our results show that curcumin can significantly reduce the expression and activity of MMP-2 and MMP-9. Because of the anti-inflammatory effects of curcumin, this compound can be considered as a new strategy for the prevention of cardiovascular events.

Matrix metalloproteinases (MMPs) are involved in the remodelling of the glomerularbasement membrane (GBM) by tightly regulating the metabolism of extracellular matrix (ECM)
of the GBM. Directory of Open Access Journals (DOAJ), Google Scholar, PubMed,EBSCO, Scopus and Web of Science have been searched. Gelatinases (MMP-2 and MMP-9) are mainly found involved in the remodelling of GBM and therefore this review focuses on these two MMPs and their action in nephrotic syndrome (NS),
which is a protein losing enteropathy occurring due to the loss of integrity of GBM. In addition to the blood corpuscles, glomerular epithelial cells and mesangium are also expressing MMPs, and various cytokines and growth factors are involved in addition to tissue inhibitors of metalloproteinases (TIMPs) in regulating the metabolism of ECM via MMPs. While examining the results of
MMP activity and expression in NS, except diabetic nephropathy (DN), membranoproliferative glomerulonephritis (MPGN) and hereditary NS where there was a clear down-regulation of MMP,
all the other types of NS showed conflicting results. Both suppression and induction of MMPs are finally leading to GBM thickening, loss of integrity and proteinuria. Enhanced MMP activity leads
to increase in matrix turnover and accumulation of ECM remnants and apoptotic cells leading to fibrosis. On the other hand, diminished expression of MMPs prevents the normal ECM turnover
and matrix accumulation. The review compiled the mechanisms of action of both downregulation and upregulation of MMPs.

Imbalance of ECM metabolism due to varied expression levels and activities of MMPs in different types of primary NS might contribute to the progression of nephropathies. Further studies are required to identify the potential and usage of MMPs as a diagnostic/prognostic/ therapeutic tool.

The prominent hallmark of malignancies is the metastatic spread of cancer cells. Recent studies have reported that the nature of invasive cells could be changed after this phenomenon, causing chemotherapy resistance. It has been demonstrated that the up-regulated expression of matrix metalloproteinase (MMP) 2/MMP-9, as a metastasis biomarker, can fortify the metastatic potential of leukemia. Furthermore, investigations have confirmed the inhibitory effect of cannabinoid and endocannabinoid on the proliferation of cancer cells in vitro and in vivo. In the present study, the inhibitory effect of WIN 55212-2 (a CB1/CB2 receptor agonist) and AM251 (a selective CB1 receptor antagonist) on K562 cells, as a chronic myelogenous leukemia (CML) model, was evaluated using MTT and invasion assay. Expressions of MMP-2 and MMP-9 were then assessed by Western blot analysis. The data obtained from MTT assay showed that WIN 55212-2 could attenuate cell proliferation; however, AM251 was less effective in this regard. Our results showed that WIN 55212-2 considerably reduced cancer cell invasiveness, while AM251 exhibited a converse effect. Moreover, CB1 activation resulted in decreased expression of MMP-2 and MMP-9. Our findings clarifies that CB1 receptors are responsible for anti-invasive effects in the K562 cell line.

Gender medicine is a new era of science which focuses on the impact of sex hormones and gender on normal physiology, pathobiology and clinical features of diseases. In this study we investigated the impact of pregnancy doses of progesterone hormone on the expression of a couple of matrix metalloproteinase (MMPs), which are known to be involved in tissue remodeling of lungs in health and disease, namely MMP7 and 13. Pregnancy maintenance dose of progesterone was administered to female BALB/c mice for 21 and 28 days, the control group received PBS for the same days. After removal of the lungs and RNA extraction, quantitative real-time PCR was done using specific primers for MMP7 and MMP13. We found that progesterone can slightly (not significantly) decrease the expression of MMP13 but had no effect on MMP7. Our results shows that progesterone has minimal effect on the expression of matrix metalloproteinase7 and matrix metalloproteinase 13, but it may still have an effect on corresponding tissue inhibitor of matrix metalloproteinases (TIMPs) or other components of the Extracellular matrix which remains to be elucidated. Also, the effect of progesterone on these MMPs can be further studied in a fibrosis model.

Angiogenesis is the formation of new blood capillaries, and it is important for physiological processes such as growth and development and pathological conditions such as tumor growth and metastasis. Angiogenesis inhibition is considered very useful in the prevention and treatment of cancer. Matrix metalloproteinases (MMPs) are a family approximately consists of 28 zinc-dependent content endopeptidase which degrade the extracellular matrix (ECM) and play an important role on angiogenesis development and tumor metastasis. Therefore, inhibition of MMPs prevents the angiogenesis. The expression and levels of MMP-2 and MMP-9 is increased in many human tumors, including ovarian, breast and prostate tumors. In this study, cytotoxic effects of (Z)-3-((5-(benzylthio)-4H-1,2,4-triazol-3-yl)imino)-5-haloindolin-2-one derivatives 1a-1l were evaluated in MCF-7 (human breast adenocarcinoma) cell line by MTT assay. Then, the potency of the tested of some synthesized compounds was evaluated on supernatants activities and levels of MMP-2 and MMP-9 by gelatin zymography and ELISA methods. Among the tested compounds, 1j, 1l and 1k had the greatest cytotoxicity against MCF-7 cell line compared to the positive (sunitinib) and negative (DMSO) controls. Moreover, our observations indicated that the compounds 1j, 1l and 1k decreased the supernatants activities of MMP-2 and MMP-9 more than others and all of the tested compounds considerably decreased the supernatants levels of MMP-9. Finally, our findings suggest that the tested derivatives are probably able to inhibit macromolecules like MMPs which have essential role in angiogenesis pathway.

Introduction. Cardiovascular disease (CVD) is the main cause of death in children with end-stage renal disease (ESRD). Matrix metalloproteinases (MMP-2 and MMP-9) are members of endopeptidases which contribute to CVD. The aim of this study was to evaluate the association of MMP-2 and MMP-9 with markers of endothelial dysfunction, soluble E-selectin and brachial flow-mediated dilatation; several biochemical risk factors of CVD; and thrombotic incidents in children with ESRD.
Materials and Methods. Thirty-one children with ESRD and 18 healthy age- and sex-adjusted controls underwent measurement of serum levels of MMP-2, MMP-9, soluble E-selectin, phosphorus, calcium, parathyroid hormone, lipid profile, thrombotic factors, and albumin. Flow-mediated dilatation was measured in both groups by Doppler ultrasonography. Thrombotic events were assessed in patients with ESRD.
Results. Matrix metalloproteinase-2 positively correlated with systolic and diastolic blood pressure, soluble E-selectin, creatinine, cholesterol, triglyceride, low-density lipoprotein cholesterol, phosphorus, and parathyroid hormone and negatively correlated with body mass index, hemoglobin, high-density lipoprotein cholesterol, and flow-mediated dilatation, while MMP-9 correlated with soluble E-selectin, phosphorus, parathyroid hormone, and albumin and negatively correlated with body mass index and hemoglobin. Six patients (19.3%) had thrombotic incidents. There was no significant difference between the levels of MMP-2 and MMP-9 in the children with and without thrombotic events.
Conclusions. This study determined the associations of MMP-2 and MMP-9 with markers of endothelial dysfunction and several traditional and uremia related CVD risk factors in children with ESRD. No associations were found between these two MMPs and thrombotic events.

Upregulation of matrix metalloproteinases (MMPs), in particular MMP-2 and MMP-9 contributes to secondary pathogenesis of spinal cord injury (SCI) via promoting inflammation. Recently, we reported that trehalose suppresses inflammatory responses following SCI. Therefore, we investigated the effect of trehalose on MMP-2 and MMP-9 expression in SCI. A weight-drop contusion SCI was induced in male rats. Then, animals received trehalose at three doses of 10 (T10), 100 (T100) and 1000 (T1000) mM intrathecally. MMP-2 and MMP-9 transcripts were then measured in damaged spinal cord at 1, 3 and 7 days after trauma, and compared with vehicle and sham groups. Additionally, behavioral analysis was conducted for 1 week using Basso-Beattie-Bresnahan (BBB) locomotor rating scale. Our data showed an early upregulation of MMP-9 at 1 day post-SCI. However, MMP-2 expression was increased at 3 days after trauma. Treatment with 10 mM trehalose significantly reduced MMP-2 expression at 3 and 7 days (P

Considering the bioactivities exhibited by microalgae, the effect of protein extract of Chlorella minutissimma (CP extract) was investigated on the expression of human matrix metalloproteinases-1 (MMP-1) in the breast cancer cell line MDA-MB231, and that of MMP-2 and -9 in hepatocellular cancer cell line HepG2 at different expression levels. The study aimed identification and analysis of inhibitory activity of microalgal components extracted from Chlorella minutissima against human MMPs.
In this experimental study, we analysed the effect of Chlorella extracts on MMP-1, -2, and -9 expression at various levels. Gelatin zymography was performed to study the inhibitory effect of Chlorella exracts on human gelatinases at the activity level, followed by western blotting to analyse the expression of all three MMPs at the protein level. The similar effect at the mRNA level along with the probable mechanism underlying inhibition of MMPs was assessed using real-time polymerase chain reaction (PCR).
The results reveal that the treatment with CP extract decreased the mRNA expression of MMP-1, MMP-2, and MMP-9 by 0.26-, 0.29-, and 0.40-fold, respectively, at 20 μg/ml concentration as well as inhibited the activity of MMP-2 and MMP-9 by 37.56 and 42.64%, respectively, at 15 μg/ml concentration. Additionally, upregulated mRNA expression of tissue inhibitor of metalloproteinases-3 (TIMP-3) by 1.68-fold was seen in HepG2 cells at 20 μg/ml concentration treatment group. However, CP extract did not induce any change in the mRNA expression of the TIMP-1, -2 and -4 in HepG2 and TIMP-1, -2, -3 and -4 in MDA-MB231 cells. Activator protein-1 (AP-1)-dependent c-Jun-mediated transcriptional regulation of MMP-1, -2, and -9 was also studied to elucidate the appropriate mechanism involved in the inhibition of MMPs.
The CP extract successfully inhibited MMP-1, -2, and -9 at different expression levels through TIMP-3 upregulation and c-Jun downregulation.

Meningioma is one of the most common tumors of the central nervous system. It was shown that meningioma had up-regulated expression of Matrix Metalloproteinases (MMPs) that involved in cell growth, angiogenesis and metastasis.
The aim of the study was the assessment of serum MMP-2 and -9 levels in patients with different grades of meningioma.
The study included the number of 66 normal control and 101 patients with different grades of meningioma (42 cases of grade I, 38 grade II and 21 grade III). The serum samples was recruited between March 2013 and August 2017 at the Departments of neurology and neurosurgery, in an academic hospital affiliated to Guilan University of Medical Sciences, in the north of Iran. MMP-2 and -9 levels determined by Enzyme Linked Immunosorbent Assay (ELISA). All data presented are expressed as mean±Standard Error of the Mean (SEM). Statistical analysis was done using one-way ANOVA by SPSS software, version: 24.0 and only values with P≤0.05 were considered as significant
We showed that the level of MMP-2 and -9 in the serum samples of patients with meningioma was higher than in controls (P It is concluded that MMP-2 and -9 are a constant composition of human serum. It is also concluded that MMP-2 and -9 might be involved in the pathophysiology of meningioma and their detection in serum may be useful in classifying meningioma.

Matrix metalloproteinases-2 and -9 play important roles in the development of breast cancer by hydrolyzing the extracellular matrix. Since −1306C/T and −1562C/T polymorphisms are located at the promoter regions of the matrix metalloproteinase- 2 and -9 genes, respectively, C to T substitution may affect promoter activity and impact the rate of extracellular matrix degradation and cancerous cell proliferation. Therefore, we aimed to determine the genotype and allele frequencies of these polymorphisms in Iranian healthy women and women with breast cancer. We have also examined the correlation of genotypes with clinicopathological parameters such as tumor type, tumor size, and metastasis to lymph nodes.
This case-control study enrolled 200 women with breast cancer and 200 age-matched healthy women. DNA was extracted, and we determined the genotype and allele frequencies of −1306C/T matrix metalloproteinase-2 and −1562C/T matrix metalloproteinase-9 polymorphisms by the polymerase chain reaction-restriction fragment length polymorphism method. Additionally, tumor size (20 mm), tumor type (ductal/non-ductal), and metastasis (yes/no) were determined.
Genotype and allele frequencies of the −1306C/T matrix metalloproteinase- 2 polymorphism showed no significant association with the occurrence of breast cancer. Genotype and allele distribution differed in the −1562C/T matrix metalloproteinase- 9 polymorphism and indicated a 4.83-fold increase in the risk of breast cancer for T allele carriers. There was no likelihood of any interaction found between the two polymorphisms and susceptibility to breast cancer. In addition, the −1562C/T matrix metalloproteinase-9 T allele showed an association with metastasis to lymph nodes but we observed no association between the −1306C/T matrix metalloproteinase- 2 polymorphism and clinicopathological features.
The ‒1562C/T matrix metalloproteinase-9 polymorphism is involved in the pathogenesis of breast cancer in Iranian women. The T allele may increase the risk of disease.

Introduction. Diabetic nephropathy is pictured as matrix accumulation and thickening of glomerular basal membrane. Matrix metalloproteinases (MMPs) are major proteases involved in extracellular matrix degradation. Moreover, plasminogen activator inhibitor-1 (PAI-1) primarily regulates plasmin dependent proteolysis. It plays a role in renal fibrosis causing extracellular matrix accumulation through inhibition of plasmin-dependent extracellular matrix degradation. This study investigated PAI-1 serum level and MMP-3 activity and their correlation with glomerular filtration rate in patients with diabetes mellitus.
Materials and Methods. In a case-control design, serum PAI-1 concentrations and MMP-3 activity were measured in 80 patients with normoalbuminuria, microalbuminuria, and macroalbuminuria. Receiver operating characteristics curve analysis was used to assess the diagnostic accuracy of MMP-3 activity in discriminating albuminuria.
Results. In the patients with microalbuminuria, serum PAI-1 levels were higher compared with macroalbuminuric patients (P Conclusions. We found that there was a positive correlation between glomerular filtration rate and MMP-3 activity in diabetic patients. This concludes that MMP-3 may have a role in the pathogenesis of diabetic nephropathy progressions towards macroalbuminuria, and therefore, MMP-3 activity may be used in evaluating albuminuria status.