MMP-2
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Úvod do problematiky: Matrixové metaloproteinázy 2 a 9 (želatinázy, typ IV kolagenázy), patogeneticky významné produkty nádorových a zánětiivých buněk, byly v poslední době prokázány také v pohrudničních výpotcích různého původu. Zatímco se MMP-2 zdá být exprimována v pleurální tekutině konstitučně, je exprese MMP-9 indukována u patologických stavů jako jsou záněty a nádorové bujení. Údaje o stupni exprese u poruch různé etiologie jsou však rozporné. Metody: Látkové koncentrace obou želatináz byly kvantifikovány tmunochemickými metodami a metodou želatinové zymografie v tekutině 31 pohrudničních výpotků a ve 26 krevních sérech téže skupiny pacientů. Imunochemicky byly kvantifikovaný také tkáňové inhibitory metaloproteináz TIMP-1 a TIMP-2 v tekutině 39 pleurálních výpotků. Kultivační media buněk, získaných z maligních výpotků, byla testována na želatinovém filmu (n=12). Výsledky: Exprese MMP-9 (želatinázy B) v parainfekčních výpotcích byla signifikantně vyšší v porovnání s mahgními výpotky. Pro posouzení role tkáňových inhibitorů metaloproteas byly provedeny imunometrické analýzy TIMP-1 a TIMP-2 u 39 výpotků, potvrzující přednostní expresi TIMP-1 v porovnání s TIMP-2. Na rozdfl od výpotků, kde byly detegovány takřka výhradně inaktivní, proenzymové formy MMPs, kultivační media buněk, získaných z mahgních výpotků, byly v řadě případů proteolyticky aktivní při přímém želatinovém testu, což nasvědčuje přítomnosti volných aktivovaných proteas. Závěry: Uvedené výsledky jsou příspěvkem k objasnění vztahů mezi expresí proteas/antiproteas v pohrudničnich výpotcích a etiologií pleurálních poruch. Fenotypová různorodost exprese proteas u maligních výpotků vyžaduje však další studium, jehož cílem je rozšíření informačního potenciálu pleurálních tekutin.
Background: Matrix metalloproteinases 2 and 9 (gelatinases, type IV collagenases), pathogenetically important products of tumor and inflammatory cells, have previously been detected in pleural effusions of different origin. Whereas MMP-2 appeared to be expressed in pleural fluids constitutively, the expression of MMP-9 is apparently induced under pathological conditions, such as inflammation and cancer. However, the reports on the degree of expression of MMP-9 in effusions of different etiology remain contradictory. Methods: The expression of gelatinase A and B was quantified on the basis of molar concentration by means of immunoassays and gelatin zymography in 31 pleural effusion fluids, and in 26 sera from the same patient group. Tissue inhibitors of metalloproteinases TIMP-1 and TIMP-2 were analyzed by immunoassays in 39 effusions. Cultivation media of malignant effusion-derived cells were tested by a gelatin film method (n = 12). Results: The expression of MMP-9 (gelatinase B) in parainflammatory effusions was found to be significantiy higher when compared to parsmeoplastic effusions. To assess the regulatory role of tissue inhibitors of metalloproteinases, TIMP-1 and TIMP-2 in 39 effusions were subjected to immunometric qucintification, confirming high expression of TIMP-1 when compared to TlMP-2. In contrast to pleural fluids, in which almost exclusively inactive, proenzyme forms of MMPs were detected, some of the cultivation media of malignsoit effusion-derived cells weproteolytically active against a gelatin film, indicating the presence of free activated proteases. Conclusions: The results contribute to the understanding correlations between the expression of proteinases/antiproteinases and etiology of pleural disorders. To explore phenotypically heterogenous expression of proteases in mahgnant effusions, further investigation is needed, aiming at the extension of the informative potential of pleural fluids.
- MeSH
- dospělí MeSH
- finanční podpora výzkumu jako téma MeSH
- imunochemie metody MeSH
- lidé středního věku MeSH
- lidé MeSH
- maligní pleurální výpotek diagnóza patologie MeSH
- matrixová metaloproteinasa 2 krev MeSH
- matrixová metaloproteinasa 9 krev MeSH
- pleurální výpotek diagnóza patologie MeSH
- senioři MeSH
- tkáňové inhibitory metaloproteinas krev MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- přehledy MeSH
- srovnávací studie MeSH
- MeSH
- finanční podpora výzkumu jako téma MeSH
- geny genetika imunologie MeSH
- interpretace statistických dat MeSH
- klinické laboratorní techniky využití MeSH
- lidé MeSH
- matrixová metaloproteinasa 2 genetika imunologie MeSH
- polymorfismus genetický genetika imunologie MeSH
- revmatoidní artritida etiologie genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- srovnávací studie MeSH
Úvod: Preeklampsie je onemocnění, které ohrožuje na životě matku I plod. Na celém světě je každý rok diagnostikováno u 10 milionů žen, což odpovídá 3–8 % všech těhotenství. V současné době nemá preeklampsie prokázanou účinnou léčbu. To zdůrazňuje potřebu předpovědi této komplikace. Tato prospektivní studie se provádí za účelem stanovení, zda mají matrixové metaloproteinázy-2 a -9 prognostický význam jako časné markery preeklampsie. Materiály a metody: Hladiny matrixových metaloproteináz-2 a -9 byly hodnoceny u 72 pacientek. U 34 z nich se následně v průběhu těhotenství vyvinula preeklampsie (u 20 pacientek mírná forma, u 14 pacientek těžká forma). Tyto pacientky představovaly základní skupinu. Kontrolní skupinu tvořilo 38 pacientek. Výsledky: U těhotných žen, u nichž se následně vyvinula preeklampsie, byla hladina matrixové metaloproteinázy-2 v 11.–13. týdnu těhotenství 155 ± 73,4 ng/ml a byla významně vyšší než úroveň u těhotných žen bez hypertenzních poruch (75,0 ± 32,8 ng/ml). Prováděná studie prokazuje významně nižší koncentraci matrixové metaloproteinázy 9 u těhotných žen s preeklampsií v porovnání s kontrolní skupinou (749 ± 296 ng/ml vs. 1 667 ± 552 ng/ml; p < 0,001). Provedený výzkum ukazuje, že v prvním trimestru byla mezní hodnota matrixové metaloproteinázy-2 pro predikci rozvoje preeklampsie ≥ 102 ng/ml (senzitivita 88,24 % a specificita 82,76 %). V případě matrixové metaloproteinázy-9 předpovídala v prvním trimestru rozvoj preeklampsie hladina ≤ 980 ng/ml se senzitivitou 85,29 % a specificitou 84,48 %. Závěr: Studie stanovila mezní hodnoty matrixových metaloproteináz-2 a -9 v prvním trimestru pro předpověď rozvoje preeklampsie.
Introduction: Preeclampsia is a life-threatening condition for the mother and foetus. Globally, it is diagnosed in 10 mil. women every year, which accounts for 3% to 8% of all pregnancies. Currently there is no proven effective treatment for preeclampsia. The aforesaid text actualises the issue of predicting this complication. To determine the prognostic significance of matrix metalloproteinases-2 and -9 levels as early markers of preeclampsia, the present prospective study was conducted. Materials and methods: The levels of matrix metalloproteinases-2 and -9 were assessed in 72 patients. Thirty-four of them subsequently developed preeclampsia during pregnancy (20 patients with moderate preeclampsia, 14 patients with severe preeclampsia), and constituted the basic group; 38 patients made up the control group. Results: In pregnant women with the subsequent development of preeclampsia, the level of matrix metalloproteinase-2 at 11–13 weeks of gestation was 155 ± 73.4 ng/mL and significantly exceeded its level in pregnant women without hypertensive disorders – 75.0 ± 32.8 ng/mL. The study conducted demonstrates a significantly lower concentration of matrix metalloproteinase-9 in pregnant women with preeclampsia compared to the control – 749 ± 296 ng/mL and 1,667 ± 552 ng/mL (P < 0.001). The performed research figures that in the first trimester, the cut-off value of matrix metalloproteinase-2 for predicting the development of preeclampsia is ≥ 102 ng/mL (sensitivity 88.24% and specificity 82.76%). For matrix metalloproteinase-9, a level of ≤ 980 ng/mL in the first trimester predicts the development of preeclampsia with a sensitivity of 85.29% and a specificity of 84.48%. Conclusion: The study established the cut-off values of matrix metalloproteinases-2 and -9 for predicting the development of preeclampsia in the first trimester.
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.
- 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
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
- centrální nervový systém fyziologie imunologie MeSH
- elektroforéza v polyakrylamidovém gelu metody využití MeSH
- interferon beta chemie imunologie MeSH
- interpretace statistických dat MeSH
- magnetická rezonanční tomografie metody využití MeSH
- matrixová metaloproteinasa 2 chemie imunologie MeSH
- matrixová metaloproteinasa 9 chemie imunologie MeSH
- roztroušená skleróza farmakoterapie 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
BACKGROUND: The matrix metalloproteinases (MMP) are a family of proteolytic enzymes involved in tumor growth and in the process of invasion. The aim of our study was to test the levels of MMP-2, MMP-7, and the MMP inhibitors TIMP-1 and TIMP-2 mRNA in colorectal carcinoma tissue samples with the clinicopathological status of the disease. PATIENTS AND METHODS: Colorectal carcinoma tissue samples were obtained from 38 patients who underwent resection of colorectal carcinoma. The expression levels of mRNA of MMP-2, MMP-7, TIMP-1, TIMP-2 and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as a housekeeping gene were quantified in these tissue samples using the method of reverse transcription real-time PCR. RESULTS: It was found that the levels of mRNA expression of MMP-2, TIMP-2, MMP-7 and TIMP-1 were significantly higher in tumor tissue samples than in the normal colorectal tissue (p < 0.0020, p < 0.0467, p < 0.0007 and p < 0.0003 respectively). The level of mRNA expression of MMP-2, MMP-7, TIMP-2 and TIMP-1 did not correlate with the stage of the disease, localization of the tumor, metastatic spread or with disease-free survival (DFI). We recorded a statistically significant inverse negative correlation (r = -0.85; p < 0.0001) between the levels of MMP-7 mRNA and TIMP-2 mRNA. Correlations between the values of mRNA MMP-7 vs. TIMP-1, MMP-2 vs. TIMP-2, MMP-2 vs. TIMP-1 and MMP-2 vs. MMP-7 were not statistically significant. CONCLUSION: We found that there were statistically significant differences in the levels of MMP-2, MMP-7, TIMP-1, TIMP-2 mRNA between normal colorectal tissue and tumor tissue, but we did not find any statistically significant correlation between mRNA levels of MMP-2, MMP-7, TIMP-1, TIMP-2 expression and localization of tumor, clinical stage or course of disease. We found an inverse negative statistically significant correlation between mRNA levels of MMP-7 and TIMP-2. On the basis of these results the clinical use of this approach to the determination of a prognosis is ambiguous.
- MeSH
- dospělí MeSH
- exprese genu MeSH
- financování organizované MeSH
- kolorektální nádory metabolismus mortalita patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- matrixová metaloproteinasa 2 biosyntéza MeSH
- matrixová metaloproteinasa 7 biosyntéza MeSH
- messenger RNA analýza MeSH
- nádorové biomarkery analýza MeSH
- polymerázová řetězová reakce s reverzní transkripcí MeSH
- přežití bez známek nemoci MeSH
- prognóza MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- stanovení celkové genové exprese MeSH
- tkáňový inhibitor metaloproteinasy 1 biosyntéza MeSH
- tkáňový inhibitor metaloproteinasy 2 biosyntéza MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři nad 80 let MeSH
- senioři 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
BACKGROUND: An essential step in the process of tumor invasion and metastasis involves the degradation of tissue barriers in the extracellular matrix (ECM), particularly in the basal membrane (BM). Matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs), in particular MMP-2, MMP-7, TIMP-1 and TIMP-2, play an important role in the process of ECM and BM degradation in connection with tumor invasion. The aim of our study was to assess the levels of MMP-2, MMP-7, TIMP-1 and TIMP-2 mRNA expression in colorectal carcinoma tissue samples and to correlate them with the stage of the disease. PATIENTS AND METHODS: The study included samples of tumor tissue of 38 patients with colorectal carcinoma and samples of tissue of 11 patients with benign disease. The expression levels of mRNA MMP-2, MMP-7, TIMP-1, TIMP-2 and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), as housekeeping gene, were quantified in tissue samples using the method of reverse transcription real-time PCR. RESULTS: The levels of mRNA expression of MMP-2, MMP-7 and TIMP-1 were significantly higher in tumor tissue samples that in the control tissue (p<0.0005, p<0.0007 and p<0.0004). In addition the presence of mRNA MMP-2, MMP-7, TIMP-1 and TIMP-2 in tumor tissue samples in these parameters was significantly higher than in the control tissue (p<0.003, p<0.0001, p<0.0001 and p<0.05). CONCLUSION: This pilot study demonstrated that a significant difference in the level and in the presence of mRNA MMP-2, MMP-7 and TIMP-1 expressions between tumor colorectal and control colorectal tissues might be helpful for the prognosis of colorectal cancer.
- MeSH
- dospělí MeSH
- financování vládou MeSH
- kolorektální nádory enzymologie genetika patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- matrixová metaloproteinasa 7 biosyntéza genetika MeSH
- messenger RNA biosyntéza genetika MeSH
- polymerázová řetězová reakce MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- staging nádorů MeSH
- tkáňový inhibitor metaloproteinasy 1 biosyntéza genetika MeSH
- tkáňový inhibitor metaloproteinasy 2 biosyntéza genetika MeSH
- želatinasy biosyntéza genetika MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři nad 80 let MeSH
- senioři MeSH