MT1-MMP (MMP-14) is a multifunctional protease that regulates ECM degradation, activation of other proteases, and a variety of cellular processes, including migration and viability in physiological and pathological contexts. Both the localization and signal transduction capabilities of MT1-MMP are dependent on its cytoplasmic domain that constitutes the final 20 C-terminal amino acids, while the rest of the protease is extracellular. In this review, we summarize the ways in which the cytoplasmic tail is involved in regulating and enacting the functions of MT1-MMP. We also provide an overview of known interactors of the MT1-MMP cytoplasmic tail and the functional significance of these interactions, as well as further insight into the mechanisms of cellular adhesion and invasion that are regulated by the cytoplasmic tail.

• Klíčová slova
• MT1-MMP, cell invasion, intracellular trafficking, matrix metalloproteinases, post-translational modifications,
• MeSH
• buněčná adheze MeSH
• matrixová metaloproteinasa 14 * metabolismus   MeSH
• pohyb buněk MeSH
• signální transdukce * MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• matrixová metaloproteinasa 14 * MeSH

Membrane-type metalloproteinases (including MMP-14 and MMP-15) are enzymes involved in the degradation of extracellular matrix components. In cancer, they are involved in processes such as cellular invasion, angiogenesis and metastasis. Therefore, the aim of this study was to evaluate the expression, content and activity of MMP-14 and MMP-15 in human renal cell carcinoma. Samples of healthy kidney tissue (n = 20) and tissue from clear-cell kidney cancer (n = 20) were examined. The presence and contents of the MMPs were assessed using Western blot and ELISA techniques, respectively. Their activity-both actual and specific-was evaluated using fluorimetric analysis. Both control and cancer human kidney tissues contain MMP-14 and MMP-15 enzymes in the form of high-molecular-weight complexes. Moreover, these enzymes occur in both active and latent forms. Their content in cancer tissues is very similar, but with a noteworthy decrease in content with an increase in the kidney cancer grade for both membrane-type metalloproteinases. Even more notable is the highest content of the investigated enzymes represented by MMP-14 in the control tissues. Considering the actual and specific activity outcomes, MMP-14 dominates over MMP-15 in all of the investigated tissues. Nevertheless, we also noted a significant enhancement of the activity of both metalloproteinases with an increase in the grade of renal cancer. The expression and activity of both enzymes were detected in all examined renal cancer tissues. However, our findings suggest that transmembrane metalloproteinase 14 (MMP-14) plays a much more significant and essential role than MMP-15 in the studied renal carcinoma tissues. Therefore, it seems that MMP-14 could be a promising target in the diagnosis, prognosis and therapy of renal cell carcinoma.

• Klíčová slova
• MMP-14, MMP-15, cancer, renal carcinoma, transmembrane metalloproteinases,
• MeSH
• dospělí MeSH
• karcinom z renálních buněk * metabolismus   patologie   enzymologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• matrixová metaloproteinasa 14 * metabolismus   MeSH
• matrixová metaloproteinasa 15 * metabolismus   genetika   MeSH
• nádory ledvin * patologie   metabolismus   enzymologie   MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Názvy látek
• matrixová metaloproteinasa 14 * MeSH
• matrixová metaloproteinasa 15 * MeSH
• MMP14 protein, human MeSH Prohlížeč
• MMP15 protein, human MeSH Prohlížeč

INTRODUCTION: Matrix metalloproteinase (MMP) belonging to family of zinc-dependent endopeptidases participates in remodelling of extracellular matrix in many physiological and pathological processes including rheumatoid arthritis (RA). Rheumatoid arthritis is a chronic autoimmune inflammatory multi-systemic disease characterized, among others, by degradation of hyaline articular cartilage and escalated angiogenesis. As a matter of fact, these processes may by influenced by MMP. On the other hand, MMP can suppress inflammation by degrading biologically active molecules like cytokines, chemokines or growth factor receptors. Increased levels of MMP-2 (gelatinase A) are observed in serum and synovial fluid of patients with RA. Gene polymorphism for MMP-2 can affect susceptibility to development and/or severity of RA. METHOD: The aim of the study was to prove possible association of polymorphisms in gene promotor region for MMP-2 (-1575 G/A, -1306 C/T, -790 T/G, -735 C/T) with RA. We worked with 101 patients with RA who met reviewed diagnostic criteria of ACR (1987) for RA, and suffer from RA for at least 2 years. Control group consisted of 101 healthy volunteers of similar age and gender distribution. RESULTS: RA patients and control group did not differ in genotype distributions or frequencies of alleles of polymorphisms -1575A/G, -1306C/T and -735 C/T. Significant difference was observed between RA patients and control group in allelic frequencies of polymorphism -790 T/G MMP-2 (T allele -0.70 vs. 0.66, Pa = 0.013). Also, a tendency of GG genotype growth was noted in RA patients (Pg = 0.053). Significant difference in allelic frequencies was also observed between men with RA and men from control group (T allele -0.80 vs. 0.61, Pa = 0.025). Haplotype of GCGC polymorphisms -1575 G/A, -1306 C/T, 790 T/G, -735 C/T was more frequent in RA patients (Pcorr = 0.016; OR = 0.09; confidence interval 0.00-0.65), whereas GCTC haplotype was noted more frequently in control group (Pcorr = 0.017; OR = 1.8; confidence interval 1.17-2.70). CONCLUSION: The results indicate the association between polymorphisms in gene promotor region for MMP-2 and susceptibility to development of RA.

• MeSH
• dospělí MeSH
• genetická predispozice k nemoci MeSH
• lidé středního věku MeSH
• lidé MeSH
• matrixová metaloproteinasa 2 genetika   MeSH
• polymorfismus genetický * MeSH
• promotorové oblasti (genetika) genetika   MeSH
• revmatoidní artritida genetika   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• Názvy látek
• matrixová metaloproteinasa 2 MeSH

MMP-2 and MMP-9 play a significant role in the development of numerous diseases mainly with the inflammatory pathogenesis. One of the drugs exerting an effect on metalloproteinases is IFN-beta. Previous studies showed that IFN beta-1b can decrease MMP synthesis and moreover inhibit their proteolytic activity. The aim of our study was to analyse the influence of recombinant IFN beta-1a (identical with natural IFN-beta) on MMP-2 and MMP-9 activities. The gelatinolytic activity was evaluated with zymography in sera obtained from 10 healthy donors. After electrophoresis gels were incubated with or without IFN beta-1a (2000 U/ml) for 18 h. We noticed a significant decrease of MMP-2/72 kDa (P = 0.0283) and the augmentation of MMP-9/92 kDa (P = 0.0042) activities after incubation with interferon. The elevation of MMP-9/92 kDa activity suggests that IFN beta-1a can exhibit proinflammatory features besides well-known anti-inflammatory properties.

• MeSH
• dospělí MeSH
• interferon beta 1a MeSH
• interferon beta farmakologie   MeSH
• lidé MeSH
• matrixová metaloproteinasa 2 metabolismus   MeSH
• matrixová metaloproteinasa 9 metabolismus   MeSH
• posttranslační úpravy proteinů účinky léků   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• interferon beta 1a MeSH
• interferon beta MeSH
• matrixová metaloproteinasa 2 MeSH
• matrixová metaloproteinasa 9 MeSH

Matrix metalloproteinases (MMP)-2 and MMP-9 play important roles in inflammation as well as in pain processes. For this reason, we compared the concentrations of these enzymes in skin and serum of patients with complex regional pain syndrome (CRPS), other pain diseases and healthy subjects. We analyzed ipsi- and contralateral skin biopsies of 18 CRPS patients, as well as in 10 pain controls and 9 healthy subjects. Serum samples were analyzed from 20 CRPS, 17 pain controls and 17 healthy subjects. All samples were analyzed with ELISA. Concentrations were then compared to clinical data as well as to quantitative sensory testing data.MMP-2 was increased in both ipsi- and contralateral skin biopsies of CRPS patients compared to healthy subjects. While low ipsilateral MMP-2 was associated with trophic changes, contralateral MMP-2 inversely correlated with the CRPS severity. MMP-9 was also locally increased in ipsilateral CRPS skin, and higher ipsi- and contralateral MMP-9 levels correlated with CRPS severity. We conclude that MMP-2 and MMP-9 are differently expressed depending on the clinical phenotype in CRPS. PERSPECTIVE: This article describes an upregulation of MMPs in CRPS and pain controls and shows different expression of MMP-2 and -9 depending on clinical phenotype in CRPS. These results provide evidence that MMP-2 and -9 play a key role in CRPS pathophysiology.

• Klíčová slova
• Complex regional pain syndrome, Complex regional pain syndrome severity score, inflammation, matrix metalloproteinases, pain,
• MeSH
• biopsie MeSH
• dospělí MeSH
• komplexní regionální syndromy bolesti metabolismus   patofyziologie   MeSH
• kůže MeSH
• lidé středního věku MeSH
• lidé MeSH
• matrixová metaloproteinasa 2 metabolismus   MeSH
• matrixová metaloproteinasa 9 metabolismus   MeSH
• stupeň závažnosti nemoci MeSH
• zánět metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• matrixová metaloproteinasa 2 MeSH
• matrixová metaloproteinasa 9 MeSH
• MMP2 protein, human MeSH Prohlížeč
• MMP9 protein, human MeSH Prohlížeč

The purpose of this study was to determine the production of metalloproteinases (MMP) 2 and 9 following UV-B irradiation in human corneal epithelial cells and fibroblasts. Epithelial cells and fibroblasts were separated from human donor corneas and exposed to UV-B lamp irradiation for 20, 40, 80 and 120 s. Media samples were collected at 8, 24, 48 and 72 h and gelatinase A and B production was assayed by the ELISA test. Statistical significance of production was assessed by the paired t-test. Increased production of MMP-2 was found in human corneal fibroblasts in response to UV-B irradiation. A statistically significant production of MMP-2 was not observed in human corneal epithelial cells following UV-B exposure. We did not detect any increase in MMP-9 after irradiation in either epithelial cells or fibroblasts. MMP-2 is produced by the corneal fibroblasts in the acute phase after UV-B irradiation. MMP-9 is not released in vitro following UV-B irradiation damage and therefore does not directly participate in the pathophysiology of acute photokeratitis.

• MeSH
• dávka záření MeSH
• fibroblasty metabolismus   účinky záření   MeSH
• kultivované buňky MeSH
• lidé MeSH
• matrixová metaloproteinasa 2 biosyntéza   MeSH
• matrixová metaloproteinasa 9 biosyntéza   MeSH
• rohovka metabolismus   účinky záření   MeSH
• rohovkový epitel metabolismus   účinky záření   MeSH
• techniky in vitro MeSH
• ultrafialové záření * MeSH
• vztah dávky záření a odpovědi MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• matrixová metaloproteinasa 2 MeSH
• matrixová metaloproteinasa 9 MeSH

The influence of polymorphisms in the large group of MMP and TIMP genes on clinical outcomes in patients after ST elevation myocardial infarction (STEMI) treated with primary PCI was analysed. In total, 550 consecutive Caucasian patients with STEMI were included in the present study, with a median of 32 months. We analysed 19 polymorphisms in the genes coding MMP and TIMP genes. The MMP-1 -519A/G and -422A/T polymorphisms are associated with combined endpoint after myocardial infarction. The hazard ratio for AT variant of MMP-1 -422A/T was 1.75 (p < 0.001); the variants with at least one A allele of MMP-1 -519A/G have less risk of combined endpoint. The TT variants of -1562C/T MMP-9 and at least one T allele of +92C/T MMP-13 were considered in a trend to affect disease progression and long-term survival after myocardial infarction. According to reclassification analysis NRI and IDI, long-term risk stratification using MMP-1 -422A/T and -519A/G polymorphisms gives additional information to the commonly used GRACE risk score. Patient stratification after myocardial infraction (MI) according to risk genotypes of MMP-1 polymorphisms could have important clinical implications for identification of patients at risk and therapeutic strategies.

• Klíčová slova
• MMP, Polymorphism, Prognosis, STEMI, TIMP,
• MeSH
• alely MeSH
• dospělí MeSH
• infarkt myokardu s elevacemi ST úseků diagnóza   genetika   MeSH
• koronární angioplastika MeSH
• lidé středního věku MeSH
• lidé MeSH
• matrixová metaloproteinasa 1 genetika   MeSH
• matrixová metaloproteinasa 13 genetika   MeSH
• matrixová metaloproteinasa 9 genetika   MeSH
• polymorfismus genetický MeSH
• prognóza MeSH
• rizikové faktory MeSH
• senioři MeSH
• tkáňové inhibitory metaloproteinas genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• matrixová metaloproteinasa 1 MeSH
• matrixová metaloproteinasa 13 MeSH
• matrixová metaloproteinasa 9 MeSH
• MMP1 protein, human MeSH Prohlížeč
• MMP13 protein, human MeSH Prohlížeč
• MMP9 protein, human MeSH Prohlížeč
• tkáňové inhibitory metaloproteinas MeSH

Levels of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9) and tumor necrosis factor-α (TNF-α) may influence wound healing and wound closure in non-healing wounds. The aim of the study was to test the hypothesis that hydrogencalcium salts of oxidized cellulose change the production of matrix metalloproteinases (MMPs) and TNF-α, wound size and number of bacterial strains in non-healing wounds. We analyzed MMP-2, MMP-9 and TNF-α in the wound fluid from 20 patients by ELISA every fourteen days over six weeks. Wound size, pain, wound closure and bacterial strains in the wound were also investigated. The wound size was reduced in 14 patients and pain in 16 patients. Bacterial contamination of the wound decreased significantly after treatment. The level of MMP-2 correlated with TNF-α production. The level of MMP-9 was unchanged during the healing period. We conclude that hydrogencalcium salts of oxidized cellulose have a favorable effect on the reduction of bacterial contamination, wound size and pain.

• MeSH
• bércové vředy metabolismus   mikrobiologie   terapie   MeSH
• celulosa oxidovaná farmakologie   MeSH
• diabetická noha metabolismus   mikrobiologie   terapie   MeSH
• hojení ran fyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• matrixová metaloproteinasa 2 metabolismus   MeSH
• matrixová metaloproteinasa 9 metabolismus   MeSH
• senioři MeSH
• TNF-alfa metabolismus   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• celulosa oxidovaná MeSH
• matrixová metaloproteinasa 2 MeSH
• matrixová metaloproteinasa 9 MeSH
• TNF-alfa MeSH

The abnormal production of matrix metalloproteinases (MMPs), especially MMP-9 and MMP-2, plays a pivotal role in hypertensive disorders of pregnancy, and as such, can influence the development of preeclampsia. These alterations may result from functional genetic polymorphisms in the promoter region of MMP-9 and MMP-2 genes, which modify MMP-9 and MMP-2 expression. We investigated the association of MMP-9 polymorphism rs3918242 (-1562 C>T) and MMP-2 polymorphism rs2285053 (-735 C>T) with the risk of preeclampsia. This case-control study was conducted on 345 women with preeclampsia and 281 age-matched women with normal pregnancies from Tunisian hospitals. Genomic DNA was extracted from whole blood collected at delivery. Genotypes for -1562 C>T and -735 C>T polymorphisms were performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). An increased frequency of heterozygous MMP-9 -1562 C/T genotype carriers was observed in women with preeclampsia compared to healthy controls (p = 0.03). In contrast, the MMP-2 -735 C>T polymorphism was not significantly different regarding frequency distribution of the allele and genotype between healthy pregnant women and women with preeclampsia. Our study suggests that the MMP-9 -1562 C/T variant, associated with high MMP-9 production, could be a genetic risk factor for preeclampsia in Tunisian women.

• Klíčová slova
• MMP-2, MMP-9, SNPs, genotyping, preeclampsia,
• Publikační typ
• časopisecké články MeSH

Matrix metalloproteinases (MMPs) play an important role in the pathogenesis of heart failure (HF). Our aim was to determine the activities of circulating MMP-2 and MMP-9 in patients with HF in respect of gender, comorbidities and treatment (n=51). We did not reveal any differences in circulating pro-MMP-2 and pro-MMP-9 activities between the patients with HF and without it. However, there was a decrease in activity of pro-MMP-2 in treated hypertensive participants versus healthy ones. In contrast, we observed increased pro-MMP-2 activity in hypertensive participants with coexistent HF versus hypertensive participants without HF. In addition, a decrease in pro-MMP-2 activity was shown in women suffering from HF versus men suffering from HF. In conclusion, potential inhibitory effect of antihypertensive treatment on pro-MMP-2 activity was found. Coexistent HF with hypertension probably reduces the inhibitory effect of antihypertensive treatment on pro-MMP-2 activity. Our data also suggest the role of potential cardioprotective factors influencing the activity of pro-MMP-2 in women.

• MeSH
• antihypertenziva terapeutické užití   MeSH
• hypertenze krev   komplikace   farmakoterapie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• matrixová metaloproteinasa 2 krev   MeSH
• matrixová metaloproteinasa 9 krev   MeSH
• průřezové studie MeSH
• senioři MeSH
• sexuální faktory MeSH
• srdeční selhání krev   komplikace   MeSH
• studie případů a kontrol MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antihypertenziva MeSH
• matrixová metaloproteinasa 2 MeSH
• matrixová metaloproteinasa 9 MeSH
• MMP2 protein, human MeSH Prohlížeč
• MMP9 protein, human MeSH Prohlížeč