We previously demonstrated that the matrix metalloproteinase-2 (MMP-2) contained an antigenic peptide recognized by a CD8 T cell clone in the HLA-A*0201 context. The presentation of this peptide on class I molecules by human melanoma cells required a cross-presentation mechanism. Surprisingly, the classical endogenous processing pathway did not process this MMP-2 epitope.

Chronic obstructive pulmonary disease (COPD) is influenced by genetic and environmental factors. A protease-antiprotease imbalance has been suggested as a possible pathogenic mechanism for COPD. Here, we examined the relationship between circulating serpina3g, matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of metalloproteinase-1 and -2 (TIMP-1 and -2, respectively) and severity of COPD. We included 150 stable COPD patients and 35 control subjects in the study. The COPD patients were classified into four groups (I, II, III, and IV), according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines based on the severity of symptoms and the exacerbation risk. Plasma serpina3g, MMP-9, and TIMP-1 and -2 concentrations were significantly higher in the all patients than in control subjects. Plasma serpina3g, MMP-9, and TIMP-1 and -2 concentrations were significantly higher in groups III and IV than in groups I and II. A negative correlation between serpina3g, MMP-9, and TIMP-1 and -2 levels and the forced expiratory volume in 1 s (FEV1) was observed. MMP-9 concentration and the MMP-9/TIMP-1 ratio were higher in patients with emphysema than in other phenotypes (both with p < 0.01). The findings of this study suggest that circulating serpina3g, MMP-9, and TIMP-1 and -2 levels may play an important role in airway remodeling in COPD pathogenesis. Disrupted protease-antiprotease imbalance in patients with COPD is related to the presence of airway injury. MMP-9 concentration and the MMP-9/TIMP-1 ratio are the best predictors of emphysema in COPD patients.

In response to peripheral nerve injury, Schwann cells adopt a migratory phenotype and modify the extracellular matrix to make it permissive for cell migration and axonal re-growth. Uridine 5'-triphosphate (UTP) and other nucleotides are released during nerve injury and activate purinergic receptors expressed on the Schwann cell surface, but little is known about the involvement of purine signalling in wound healing. We studied the effect of UTP on Schwannoma cell migration and wound closure and the intracellular signaling pathways involved. We found that UTP treatment induced Schwannoma cell migration through activation of P2Y2 receptors and through the increase of extracellular matrix metalloproteinase-2 (MMP-2) activation and expression. Knockdown P2Y2 receptor or MMP-2 expression greatly reduced wound closure and MMP-2 activation induced by UTP. MMP-2 activation evoked by injury or UTP was also mediated by phosphorylation of all 3 major mitogen-activated protein kinases (MAPKs): JNK, ERK1/2, and p38. Inhibition of these MAPK pathways decreased both MMP-2 activation and cell migration. Interestingly, MAPK phosphorylation evoked by UTP exhibited a biphasic pattern, with an early transient phosphorylation 5 min after treatment, and a late and sustained phosphorylation that appeared at 6 h and lasted up to 24 h. Inhibition of MMP-2 activity selectively blocked the late, but not the transient, phase of MAPK activation. These results suggest that MMP-2 activation and late MAPK phosphorylation are part of a positive feedback mechanism to maintain the migratory phenotype for wound healing. In conclusion, our findings show that treatment with UTP stimulates in vitro Schwannoma cell migration and wound repair through a MMP-2-dependent mechanism via P2Y2 receptors and MAPK pathway activation.

Titin is the largest mammalian (≈3000 to 4000 kDa) and myofilament protein that acts as a molecular spring in the cardiac sarcomere and determines systolic and diastolic function. Loss of titin in ischemic hearts has been reported, but the mechanism of titin degradation is not well understood. Matrix metalloproteinase-2 (MMP-2) is localized to the cardiac sarcomere and, on activation in ischemia/reperfusion injury, proteolyzes specific myofilament proteins. Here we determine whether titin is an intracellular substrate for MMP-2 and if its degradation during ischemia/reperfusion contributes to cardiac contractile dysfunction.

Vascular calcification is a risk predictor and common pathological change in cardiovascular diseases that are associated with elastin degradation and phenotypic transformation of vascular smooth muscle cells via gelatinase matrix metalloproteinase-2 (MMP2). However, the mechanisms involved in this process remain unclear. In this study, we investigated the relationships between miR-29b-3p and MMP2, to confirm miR-29b-3p-mediated MMP2 expression at the posttranscriptional level in arterial calcification. In male Sprague Dawley rats, arterial calcification was induced by subcutaneous injection of a toxic dose of cholecalciferol. In vivo, the quantitative real-time polymerase chain reaction (qRT-PCR) showed that MMP2 expression was upregulated in calcified arterial tissues, and miR-29b-3p expression was downregulated. There was a negative correlation between MMP2 mRNA expression and miR-29b-3p levels (P = 0.0014, R2 = 0.481). Western blotting showed that MMP2 expression was significantly increased in rats treated with cholecalciferol. In vitro, overexpression of miR-29b-3p led to decreased MMP2 expression in rat vascular smooth muscle cells, while downregulation of miR-29b-3p expression led to increased MMP2 expression. Moreover, the luciferase reporter assay confirmed that MMP2 is the direct target of miR-29b-3p. Together, our results demonstrated that a role of miR-29b-3p in vascular calcification involves targeting MMP2.

Matrix metalloproteinases (MMPs) play a pathophysiological role in cancer initiation and progression. Numerous studies have examined an association between MMP-2, MMP-9, and MMP-11 expression and clinicopathological characteristics of breast cancer (BC); however, no research has been done on the MMP expression levels in BC cases from Ethiopia.

Matrix Metalloproteinases (MMPs) participate in many physiological and pathological processes. One major limitation to a better understanding of the role MMPs play in these processes is the lack of well-characterized chimeric proteins and characterization of their fluorescence. The specialized literature has reported on few constructs bearing MMPs fused to the sequence of the green fluorescent protein (GFP), but none of the described constructs have been intended for expression in bacteria or for purification and use in vivo. This work has tested a recombinant reporter protein containing the MMP-2 catalytic domain fused to GFP in terms of purification efficiency, degradation of substrates in solution and in zymograms, kinetic activity, GFP fluorescence, and GFP fluorescence in whole animals after injection of the purified and lyophilized fluorescent protein. This work has also characterized rhMMP-2 (recombinant human MMP-2) and inactive clones and used them as negative controls in experiments employing catMMP-2/GFP and rhMMP-2. To our knowledge, this is the first study that has fully characterized a chimeric protein with the MMP-2 catalytic domain fused to GFP, that has efficiently purified such protein from bacteria in a single-step, and that has obtained an adequate chimeric protein for injection in animals and tracking of MMP-2 fate and activity in vivo.

Prior study has shown that Ageratum conyzoides L. extract that containing quercetin has been proved to prevent inflammation and proteoglycan degradation by inhibiting tumor necrosis factor-alpha and matrix metalloproteinase (MMP-9) expression. Target of osteoarthritis (OA) treatment was in the synovial joint that requiring a drug delivery system. The aim of this study was to prove the efficacy of quercetin-loaded lecithin-chitosan nanoparticles on the OA model rats by observed its effect on interleukin (IL-1) β, MMP-9, MMP-13, and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS-5) expressions. In this study, 70 white male Sprague Dawley rats were divided into 14 groups, 7 groups each for destabilization of medial meniscus (DMM) and monoiodoacetate (MIA)-induced OA. After 28 days from induction, SHAM and negative group received gel base topically; positive group received sodium diclofenac gel; three-dose group received each 0.84, 1.68, 3.36 mg/g quercetin-loaded nanoparticles gel; and A. conyzoides L. group received A. conyzoides L. extract gel. Each group gets treatment until day 70, and then, blood sample was collected for serum analysis; knee joint was isolated and subjected to histology samples treatment. Quercetin-loaded nanoparticle gel dose 1 (0.84 mg/g gel), dose 2 (1.68 mg/g gel), dose 3 (3.36 mg/g), and A. conyzoides L. extract gel could decreased the level of IL-1 β, MMP-9, MMP-13, ADAMTS-5, and increasing color intensity significantly on histopathological observations on DMM and MIA-induced OA.

To determine the matrix metalloproteinase-2 (MMP-2) levels in root-canal exudates from teeth undergoing root-canal treatment.

Emerging evidence shows that exocytosis plays a key role in tumor development and metastasis. Secernin-1 (SCRN1) is a novel regulator of exocytosis. Our previous work identified SCRN1 as a tumor-associated gene by bioinformatics analysis of transcriptomes. In this study, we demonstrated the aberrant overexpression of SCRN1 at mRNA and protein level in colon cancer. We also revealed that overexpression of SCRN1 was significantly associated with the tumor development and poor prognosis. Experiments in vitro validated that SCRN1 may promote cancer cell proliferation and secretion of matrix metalloproteinase-2/9 (MMP-2/9) proteins to accelerate tumor progression.

The genome of Caenorhabditis elegans includes six homologs of matrix metalloproteinases (MMPs). The C. elegans MMP gene zmp-1 has recently been shown to be involved in anchor cell invasion during post-embryonic vulval development. Here, we identified H19M22.3 (zmp-2) as a pleiotropic MMP gene regulating disease resistance, molting, larval development, and fecundity. Zmp-2(RNAi) nematodes showed significant lifespan reduction during infection with pathogenic Photorhabdus luminescence. Moreover, we observed molting defects indicating a direct or regulative role in extracellular matrix degradation during ecdysis, delayed larval to adult development, and reduced offspring production in hermaphrodite adults. GFP-expressing nematodes revealed predominant expression of zmp-2 in multiple cells during embryogenesis; in hypodermal, muscle, and somatic gonad cells during larval development; and in developing and mature spermathecae in the L4 larval stage and adults. These results give evidence for pleiotropic roles of zmp-2 and provide novel insights into evolutionarily conserved and derived MMP functions in C. elegans.

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by destruction of bone and cartilage, which is mediated, in part, by synovial fibroblasts. Matrix metalloproteinases (MMPs) are a large family of proteolytic enzymes responsible for matrix degradation. Macrophage migration inhibitory factor (MIF) is a cytokine that induces the production of a large number of proinflammatory molecules and has an important role in the pathogenesis of RA by promoting inflammation and angiogenesis. In the present study, we determined the role of MIF in RA synovial fibroblast MMP production and the underlying signaling mechanisms. We found that MIF induces RA synovial fibroblast MMP-2 expression in a time-dependent and concentration-dependent manner. To elucidate the role of MIF in MMP-2 production, we produced zymosan-induced arthritis (ZIA) in MIF gene-deficient and wild-type mice. We found that MMP-2 protein levels were significantly decreased in MIF gene-deficient compared with wild-type mice joint homogenates. The expression of MMP-2 in ZIA was evaluated by immunohistochemistry (IHC). IHC revealed that MMP-2 is highly expressed in wild-type compared with MIF gene-deficient mice ZIA joints. Interestingly, synovial lining cells, endothelial cells, and sublining nonlymphoid mononuclear cells expressed MMP-2 in the ZIA synovium. Consistent with these results, in methylated BSA (mBSA) antigen-induced arthritis (AIA), a model of RA, enhanced MMP-2 expression was also observed in wild-type compared with MIF gene-deficient mice joints. To elucidate the signaling mechanisms in MIF-induced MMP-2 upregulation, RA synovial fibroblasts were stimulated with MIF in the presence of signaling inhibitors. We found that MIF-induced RA synovial fibroblast MMP-2 upregulation required the protein kinase C (PKC), c-jun N-terminal kinase (JNK), and Src signaling pathways. We studied the expression of MMP-2 in the presence of PKC isoform-specific inhibitors and found that the PKCdelta inhibitor rottlerin inhibits MIF-induced RA synovial fibroblast MMP-2 production. Consistent with these results, MIF induced phosphorylation of JNK, PKCdelta, and c-jun. These results indicate a potential novel role for MIF in tissue destruction in RA.

Diabetic cardiomyopathy (DM CMP) is defined as cardiomyocyte damage and ventricular dysfunction directly associated with diabetes independent of concomitant coronary artery disease or hypertension. Matrix metalloproteinases (MMPs), especially MMP-2, have been reported to underlie the pathogenesis of DM CMP by increasing extracellular collagen content.

Ischemic stroke is a complex vascular disease, which has become 1 of the major causes of morbidity and mortality worldwide. More and more data showed that matrix metalloproteinases (MMPs), in particular, MMP-2 are deleterious after ischaemic stroke. This study investigated the relationship between MMP-2 and stroke risk in the Southern Chinese population.We evaluated single nucleotide polymorphisms (SNP) of MMP-2 in stroke patients in an association study using a case-control design. Six SNPs of MMP2 were selected and genotyped by Agena MassARRAY. SNPStats, Haploview was used to analyze genetic data.Two SNPs in the MMP-2 gene were significantly associated with stroke risk.For rs1132896 (C versus G allele), the C allele was significantly reduced stroke risk (OR = 0.56, 95% confidence intervals [95% CI] = 0.39-0.81, P = .002). The effect of the T allele of rs243849 was IS risk according to an additive genetic model (OR = 0.67, 95% CI = 0.47-0.96, P = .028). We did not found any strong linkage between the six SNPs (rs1132896, rs1053605, rs243849, rs243847, rs243832, rs7201)The results presented strongly indicate that MMP-2 genetic variants are an important mediator of stroke risk.

This study was to explore the mechanisms underlying 1,2-dichloroethane (1,2-DCE) induced brain edema by focusing on alteration of matrix metalloproteinase-2 (MMP-2) in rat astrocytes induced by 2-chloroethanol (2-CE), an intermediate metabolite of 1,2-DCE in vivo. Protein and mRNA levels of MMP-2, and the phosphorylated protein levels of p38 MAPK (p-p38), extracellular signal regulated protein kinase (p-ERK1/2) and c-Jun N-terminal kinase (p-JNK1/2) in astrocytes were examined by immunostaining, western blot or real-time RT-PCR analysis. Findings from this study disclosed that protein levels of MMP-2 were upregulated by 2-CE in astrocytes. Meanwhile, protein levels of p-p38, p-ERK1/2 and p-JNK1/2 were also increased apparently in the cells treated with 2-CE. Moreover, pretreatment of astrocytes with SB202190 (inhibitor of p38 MAPK), U0126 (inhibitor of ERK1/2) or SP600125 (inhibitor of JNK1/2) could suppress the upregulated expression of p-p38, p-ERK1/2, and p-JNK1/2. In response to suppressed protein levels of p-p38 and p-JNK1/2, the protein levels of MMP-2 also decreased significantly, indicating that activation of MAPK signal pathways were involved in the mechanisms underlying 2-CE-induced upregulation of MMP-2 expression.

Matrix metalloproteinase 9 (MMP-9) plays an important role in inflammatory and pathological processes by enabling the inflow of leukocytes to the site of infection or tissue damage. MMP-9 and tissue inhibitor of metalloproteinase 1 (TIMP-1) have been described as potential prognostic biomarkers in various clinical settings. The aim of the study was to evaluate the usefulness of plasma levels of MMP-9 and TIMP-1 as well as the MMP-9/ TIMP-1 ratio in predicting the outcome in patients admitted to the intensive care unit (ICU). The study included 56 critically ill patients with multiple organ failure. Plasma levels of MMP-9 and TIMP-1 were determined on hospitalization day 1, 2, 3 and 7. Nineteen (35.7%) patients died. The level of TIMP-1 was statistically significantly higher on day 1 and 7 of hospitalization in non-survivors, as compared to survivors (p=0.01). A statistically significant positive correlation was found between MMP-9 and TIMP-1. The MMP-9/TIMP-1 ratio was comparable in both groups during of observation (0.62 on day 1). The MMP-9/TIMP-1 ratio was positively correlated with the level of lactate and negatively correlated with platelet count. Likewise, TIMP-1 was positively correlated with the level of lactate. The level of MMP-9 was higher in the non-survivor group only on day 7 of observation. In conclusion, although TIMP-1 and MMP-9 concentrations were higher in non-survivors and the MMP-9/TIMP-1 ratio was related to some parameters of critical illness, further research is needed to verify whether they can serve as reliable biomarkers for early prognostication of ICU patients.

Matrix metalloproteinase-2 (MMP-2) is involved in several physiological mechanisms, including wound healing and tumor progression. We show that MMP-2 directly stimulates dendritic cells (DCs) to both upregulate OX40L on the cell surface and secrete inflammatory cytokines. The mechanism underlying DC activation includes physical association with Toll-like receptor-2 (TLR2), leading to NF-κB activation, OX40L upregulation on DCs, and ensuing TH2 differentiation. Significantly, MMP-2 polarizes T cells toward type 2 responses in vivo, in a TLR2-dependent manner. MMP-2-dependent type 2 polarization may represent a key immune regulatory mechanism for protection against a broad array of disorders, such as inflammatory, infectious, and autoimmune diseases, which can be hijacked by tumors to evade immunity.

Regular exercise at moderate intensity reduces cardiovascular risks. Matrix metalloproteinases (MMPs) play a major role in cardiac remodeling, facilitating physiological adaptation to exercise. The aim of this study was to examine the influence of voluntary physical exercise on the MMP-2 enzyme activity and to investigate the cardiac performance by measurement of angina susceptibility of the heart, the basal blood pressure, the surviving aorta ring contraction, and the cardiac infarct size after I/R-induced injury.

Matrix metalloproteinase (MMP)-2 mediates myocardial ischemia-reperfusion injury which is characterized by enhanced peroxynitrite biosynthesis during early reperfusion. Direct infusion of peroxynitrite into isolated hearts activates MMP-2 prior to the loss in mechanical function. The mechanical dysfunction is prevented by MMPs inhibitors. MMP-2 is also found in the sarcomere of cardiomyocytes where it cleaves troponin I and myosin light chain I. Cytoskeletal proteins such as alpha-actinin, desmin and spectrin are found in close association with the sarcomere and are known to be degraded in ischemia-reperfusion injury. It remains unknown whether these proteins are degraded in peroxynitrite-induced myocardial injury and if cytoskeletal proteins are also targets for MMP-2. Peroxynitrite (80 microM) was infused into isolated rat hearts which led to a delayed onset but rapidly developing decline in mechanical function. The MMPs inhibitor PD-166793 or the peroxynitrite scavenger glutathione prevented the decline in cardiac function. At the end of perfusion, alpha-actinin levels were decreased by 45+/-3% in peroxynitrite-infused hearts as compared to control hearts; however, this was normalized to that of control hearts with either PD-166793 or glutathione. Cardiac desmin and alphaII spectrin levels were unaltered following peroxynitrite infusion. alpha-Actinin and to a lesser extent desmin are susceptible to in vitro proteolysis by MMP-2 whereas spectrin is resistant. Cardiac dysfunction induced by peroxynitrite involves degradation of alpha-actinin that may be mediated by the proteolytic action of MMP-2.

Vascular remodelling occurs during all stages of atherosclerotic progression. Anti-atherosclerotic drugs may function by restoring regulation of the processes involved in remodelling of the extracellular matrix. A key group of enzymes involved in these processes are the matrix metalloproteinases (MMPs). Oestrogens have been demonstrated to possess anti-atherosclerotic properties at low concentrations while being associated with lesion formation at high concentrations. We examined the effect of 17beta-oestradiol on MMP-2 expression in human coronary artery (CAVSMC) and umbilical artery vascular smooth muscle cells (UAVSMC). MMP-2 expression was measured by chemiluminescent immunoblotting and quantified by laser densitometry. pro-MMP-2 was secreted by VSMCs and increasing levels of 17beta-oestradiol, from physiological through supraphysiological, were associated with significant dose-dependent increases in MMP-2 levels in culture media. This effect was dependent on de novo protein synthesis and could be antagonised by the oestrogen receptor antagonist, tamoxifen, and the specific receptor antagonist ICI 182, 780. 17beta-Oestradiol appears to be a specific stimulator of MMP-2 release from human vascular cells. The concentration dependence of this effect suggests a basis for the differential effects of low and high oestrogen levels on vascular integrity.