BACKGROUND AND AIMS: Morphogenesis of the upper lip and palate is a complex process involving highly regulated interactions between epithelial and mesenchymal cells. Genetic evidence in humans and mice indicates the involvement of matrix metalloproteinases (MMPs) and their endogenous tissue inhibitors (TIMPs) in cleft lip palate (CLP) aetiology. This study investigated whether expression of MMP-2, MMP-8, MMP-9, TIMP-2, and TIMP-4, which are essential for the upper lip and palate fusion, is dysregulated in children with CLP. METHODS: Oral mucosa tissue samples were obtained from patients with complete unilateral (CU) CLP (n = 25) and complete bilateral (CB) CLP (n = 19) during corrective plastic surgery and in unaffected control subjects (n = 10). MMPs and TIMPs expression was assessed by immunohistochemistry, and the data were analyzed using the Kruskal - Wallis test with the Bonferroni correction. RESULTS: In CLP patients, MMP-2, TIMP-2 immunoreactivity in the oral mucosa was seen to have a few to abundant structures, but the overall number of MMP-2, TIMP-2-positive structures was greater than that in controls (P < 0.01). The total number of TIMP-4, MMP-9-positive cells showed a significant decrease in the CBCLP compared with that of CUCLP (P < 0.001). MMP-8 expression trends in the CLP group were similar to those of the control group. CONCLUSIONS: The results suggest that TIMP-4 and MMP-9 are the main ECM remodeling regulatory proteins expressed in CUCLP affected tissues of the oral mucosa. The increased expression of MMP-2 and TIMP-2 in CLP tissues implicates these factors in the regulation of cell migration during ECM turnover independently of different types of clefts. Investigation of MMP and TIMP expression in tissue samples from patients with CLP appears to be a promising approach to the etiopathogenesis of CLP.

• MeSH
• dítě MeSH
• extracelulární matrix metabolismus   MeSH
• lidé MeSH
• matrixové metaloproteinasy metabolismus   fyziologie   MeSH
• obličej MeSH
• předškolní dítě MeSH
• rozštěp patra etiologie   MeSH
• rozštěp rtu etiologie   MeSH
• tkáňové inhibitory metaloproteinas metabolismus   fyziologie   MeSH
• ústní sliznice metabolismus   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

The matrix metalloproteinases (MMPs) play a key role during cardiac remodeling. The aim of the study was to investigate the changes in collagenous proteins and MMPs in the model of non-ischemic, anthracycline-induced chronic cardiomyopathy in rabbits using both biochemical and histological approaches. The study was carried out in three groups of Chinchilla male rabbits: 1) daunorubicin (3 mg/kg, once weekly for 10 weeks), 2) control (saline in the same schedule), 3) daunorubicin with the cardioprotectant dexrazoxane (60 mg/kg, before each daunorubicin). Morphological changes in the myocardium of daunorubicin-treated animals were characterized by focal myocardial interstitial fibrosis of different intensity. The subsequent proliferation of the fibrotic tissue was marked by an increased content of both collagen types I and III, which resulted in their typical coexpression in the majority of bundles of fibers forming either smaller or larger scars. Biochemical analysis showed a significantly increased concentration of hydroxyproline, mainly in the pepsin-insoluble fraction of collagenous proteins, in the daunorubicin-treated group (1.42±0.12 mg/g) as compared with the control (1.03±0.04 mg/g) and dexrazoxane (1.07±0.07 mg/g) groups. Dexrazoxane co-administration remarkably reduced the cardiotoxic effects of daunorubicin to the extent comparable with the controls in all evaluated parameters. Using zymography, it was possible to detect only a gelatinolytic band corresponding to MMP-2 (MMP-9 activity was not detectable). However, no significant changes in MMP-2 activity were determined between individual groups. Immunohistochemical analysis revealed increased MMP-2 expression in both cardiomyocytes and fibroblasts. Thus, this study has revealed specific alterations in the collagen network in chronic anthracycline cardiotoxicity in relationship to the expression and activity of major MMPs.

• MeSH
• chronická nemoc MeSH
• daunomycin toxicita   MeSH
• fibróza MeSH
• financování organizované MeSH
• hydroxyprolin metabolismus   MeSH
• kardiomyopatie chemicky indukované   metabolismus   prevence a kontrola   MeSH
• kardiovaskulární látky farmakologie   MeSH
• kolagen metabolismus   MeSH
• králíci MeSH
• lékové interakce MeSH
• matrixová metaloproteinasa 2 metabolismus   MeSH
• matrixová metaloproteinasa 9 metabolismus   MeSH
• modely nemocí na zvířatech MeSH
• myokard enzymologie   patologie   MeSH
• protinádorová antibiotika toxicita   MeSH
• razoxan farmakologie   MeSH
• remodelace komor fyziologie   MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• mužské pohlaví MeSH
• zvířata MeSH

• MeSH
• chondrocyty metabolismus   patofyziologie   MeSH
• kloubní chrupavka patologie   MeSH
• matrixové metaloproteinasy MeSH
• osteoartróza MeSH
• tkáňový inhibitor metaloproteinasy 3 MeSH
• Publikační typ
• kongresy MeSH

• MeSH
• fibroblasty patologie   MeSH
• keratitida patofyziologie   MeSH
• matrixové metaloproteinasy metabolismus   MeSH
• rohovkový epitel enzymologie   MeSH
• techniky in vitro MeSH
• ultrafialové záření škodlivé účinky   MeSH

OBJECTIVE: The project was scheduled as a case-control study to investigate the correlation between MMP-2 (rs243864), MMP-9 (3918242), MMP-12 (rs7123600) and TIMP-2 (rs8176329) polymorphisms and chronic venous disease (CVD) risk. The genotype and phenotype research envisages the testing of possible associations between MMP and TIMP-2 genotypes and phenotypes of CVD. MATERIAL AND METHODS: 150 patients with CVD and 227 controls were enrolled into the study. The MMPs and TIMP-2 genotypes were identified by the PCR method and restriction analysis according to standard protocols. RESULTS: The G allele of MMP-2 -790 T/G was 1.85 times more frequent in men with CVD than in the control group (P = 0.008). The T allele of MMP-9 -1562 C/T was observed 2.571 times more frequently in patients with CVD than in the control individuals (both in men and women) with clinically significant specificity (P = 0.0000009). The G allele of MMP-12 rs7123600 was determined 2.082 times more frequently in female patients with CVD than in the control group with clinically significant specificity (P = 0.02). No significant result in TIMP-2 rs8176329 polymorphism in the case-control study was observed. CVD women with G allele in MMP-2 -790 T/G in the genotype-phenotype study are seen to develop ulceration 2.539 times more frequently (P = 0.003). The G allele of MMP-12 rs7123600 was detected 3.167 times more frequently in CVD women with ulceration compared with CVD women without ulceration (P = 0.007). In CVD men in C6 stage, the incidence of AG genotype in rs7123600 MMP-12 polymorphism was found to be 4.675 times higher compared to CVD women with C6 staging (P = 0.005). The AG genotype in TIMP 2 rs8176329 polymorphism was found to be associated with higher risk of tumour (P = 0.01). CONCLUSION: Studying these polymorphisms can contribute to better identification of patients at higher risk of developing CVD, while providing the most appropriate prevention and treatment strategies for limiting the progression and complications of CVD.

• MeSH
• chronická nemoc MeSH
• dospělí MeSH
• fenotyp MeSH
• genetická predispozice k nemoci * MeSH
• genotyp MeSH
• lidé středního věku MeSH
• lidé MeSH
• matrixové metaloproteinasy genetika   MeSH
• mladý dospělý MeSH
• polymerázová řetězová reakce MeSH
• progrese nemoci MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• tkáňový inhibitor metaloproteinasy 2 genetika   MeSH
• žilní insuficience komplikace   genetika   patologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Východisko. Matrix metaloproteázy (MMPs) patří mezi proteolytické enzymy. Jednou z jejich funkcí je i štěpení bazálních membrán buněk a extracelulární matrix. U maligních nádorů se tak mohou uplatnit v procesu invazivity a metastázování. Vznikají převážně ve stromálních buňkách (fibroblastech a endoteliích) reaktivně na přítomnost nádorových buněk. Ve vztahu k NSCLC jsou nejčastěji zmiňovány MMP-2 (gelatináza A), MMP-9 (gelatináza B) a především MMP-11 (stromelysin 3). Metody a výsledky. Zkoumali jsme vztah mezi expresí výše zmíněných matrix metaloproteáz pouze ve stromálních buňkách a 5letým přežitím u 80 nemocných po kurativní resekci pro NSCLC ve stadiu I dle TNM. Exprese MMP-2 byla asociována s 5letým přežitím, ale bez signifikantní korelace. Žádná korelace nebyla zjištěna u MMP-9. Statisticky téměř významný vztah byl zjištěn mezi expresí MMP-11 a 5letým přežitím. Závěry. Exprese MMP-11 ve stromálních buňkách kurativně zresekovaných pacientů s NSCLC v I. stadiu může být užitečná v predikci jejich prognózy.

Background. Matrix metalloproteinases (MMPs) belong to proteolytic enzymes. Degradation of the cell basement membrane and the extracellular matrix is one of their functions. In malignant tumors they can hypothetically contribute to the invasion and metastasis formation. They are mostly produced by stromal cells (fibroblasts and endothelial cells) as a response to the presence of tumor cells. MMP-2 (gelatinase A), MMP-9 (gelatinase B) and MMP-11 (stromelysin 3) are often mentioned in regard to Non-small Cell Lung Cancer (NSCLC). Methods and Results. The relation between the expression of the above-mentioned matrix metalloproteinases in stromal cells and the cancer-related survival in 80 patients after curative resection of NSCLC in stage I according to TNM was studied. The expression of MMP-2 was associated with cancer-related survival but without significant correlation. No correlation was found in MMP-9. There was a statistically near-significant relation between the expression of MMP-11 and cancer-related survival. Conclusions. The expression of MMP-11 in stromal cells in surgically treated NSCLC patients in stage I appears useful for evaluation of their prognosis.

• MeSH
• analýza přežití MeSH
• buňky stromatu metabolismus   patologie   MeSH
• finanční podpora výzkumu jako téma MeSH
• lidé MeSH
• matrixové metaloproteinasy genetika   metabolismus   MeSH
• nemalobuněčný karcinom plic chirurgie   metabolismus   MeSH
• prognóza MeSH
• Check Tag
• lidé MeSH

OBJECTIVES: to assess the relationship between maternal and umbilical serum concentrations of matrix metalloproteinases (MMP)-2,8,9, the soluble receptor for advanced glycation end products (sRAGE) and IL-10 and premature delivery and fetal inflammation. METHODS: maternal serum levels of MMPs, sRAGE, IL-10 and C-reactive protein (CRP) were determined in 67 women with preterm labor and in 38 healthy pregnant women of similar gestational age (GA). In the group with preterm labor we also determined umbilical concentrations of MMPs, IL-6 and sRAGE. The group with preterm labor was additionally divided based on the presence of funisitis and elevations of fetal umbilical IL-6 concentrations. RESULTS: maternal serum levels of MMP-2 and sRAGE were significantly lower in women with preterm labor compared to women with normal pregnancy. Additionally, within the group of women with preterm labor, maternal serum MMP-2 concentrations were significantly lower in the subgroup with funisitis and in the subgroup with elevated umbilical concentration of IL-6. CONCLUSION: our results demonstrate significantly different serum concentrations of MMP-2 and sRAGE in women with preterm labor compared to healthy pregnant patients of the same GA.

• MeSH
• C-reaktivní protein metabolismus   MeSH
• chorioamnionitida krev   enzymologie   MeSH
• fetální krev enzymologie   MeSH
• interleukin-10 metabolismus   MeSH
• lidé MeSH
• matrixové metaloproteinasy krev   MeSH
• multivariační analýza MeSH
• novorozenec MeSH
• plod MeSH
• předčasná porodní činnost krev   enzymologie   MeSH
• receptory imunologické krev   metabolismus   MeSH
• regresní analýza MeSH
• těhotenství MeSH
• Check Tag
• lidé MeSH
• novorozenec MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Cirhóza je konečné stadium chronického onemocnění jater. Vysoká morbidita a mortalita souvisejí zejména s komplikacemi vyplývajícími z portální hypertenze. Remodelace fibrotické tkáně prostřednictvím matrixových metaloproteináz (MMP) je permanentní proces, který u pacientů s cirhózou vede k cirhotické přestavbě. Cílem studie bylo posoudit význam funkčních variant genů pro metalproteinázy MMP‑1 a MMP‑7 u pacientů s cirhózou a posoudit jejich souvislost s portální hypertenzí. Pa­cienti a metody: 179 pacientů s jaterní cirhózou (střední věk 55,2 ? 11,6 let) bylo vyšetřeno na přítomnost funkčních variant genů pro MMP‑1 (-A; rs1799750) a MMP‑7 (G/A; rs17884789). U všech pacientů bylo provedeno měření gradientu tlaku v jaterních žilách, laboratorní a ultrazvukové vyšetření. Pro porovnání frekvence výskytu alel s pacienty s cirhózou zařazenými do studie byla pro zdravou populaci použita data z odborné literatury. Výsledky: Frekvence výskytu genotypů rs1799750 (1G‑1G 25 %, 1G‑2G 56 %, 2G‑2G 22 %) u pacientů s cirhózou jater a u zdravé populace se neliší (p > 0,05). V případě genu pro MMP‑7, byl u našich pa­cientů pro variantu rs17884789 zjištěn jeden genotyp (wild typ GG). Nebyla zjištěna souvislost mezi frekvencí výskytu zkoumaných genotypů a závažností portální hypertenze nebo hodnotou Child‑Pughova nebo MELD skóre. Závěr: Funkční varianty MMP‑1 a MMP‑7 nemají souvislost s portální hypertenzí u pacientů s cirhózou jater. Klíčová slova: cirhóza – fibróza – genetický polymorfizmus – matrixová metaloproteináza 1 – matrixová metaloproteináza 7 –hypertenze – portální Autoři deklarují, že v souvislosti s předmětem studie nemají žádné komerční zájmy. Redakční rada potvrzuje, že rukopis práce splnil ICMJE kritéria pro publikace zasílané do biomedicínských časopisů Doručeno: 11. 2. 2015 Přijato: 16. 3. 2015

Cirrhosis is a final stage of chronic liver disease. High morbidity and mortality are mostly related to complications of portal hypertension. Remodelling of liver fibrotic tissue by matrix metalloproteinases (MMPs) is a permanent process leading to cirrhotic scar formation. The aim was to study the significance of functional metalloproteinase MMP‑1 and MMP‑7 gene variants in cirrhotic patients and their relationship to portal hypertension. Patients and Methods: 179 patients with liver cirrhosis (mean age 55.2 ? 11.6 years) were examined for functional variants of MMP‑1 (-A; rs1799750) and MMP‑7 (G/A; rs17884789) genes. Measurement of hepatic venous pressure gradient, laboratory and ultrasound examination were performed in all patients. Literary data from a healthy population were used for comparison of allele frequencies with our cirrhotic patients. Results: The frequency of rs1799750 (1G‑1G 25%, 1G‑2G 56%, 2G‑2G 22%) genotypes in cirrhotic patients does not differ from the healthy population (p > 0.05). In MMP‑7 gene, one genotype (wild type GG) was found in our patients uniformly for rs17884789 variant. No relationship was found between the frequency of examined genotypes and either the severity of portal hypertension or Child‑Pugh or MELD score. Conclusions: Functional variants of MMP‑1 and MMP‑7 have no relationship to portal hypertension in liver cirrhosis.

• MeSH
• dospělí MeSH
• extracelulární matrix MeSH
• genotyp MeSH
• genotypizační techniky MeSH
• jaterní cirhóza * genetika   patofyziologie   MeSH
• játra krevní zásobení   patologie   MeSH
• klinické laboratorní techniky MeSH
• lidé středního věku MeSH
• lidé MeSH
• matrixové metaloproteinasy * genetika   MeSH
• portální hypertenze MeSH
• senioři MeSH
• statistika jako téma MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• práce podpořená grantem MeSH

Matrix metalloproteinases (MMPs) are a group of zinc and calcium endopeptidases which cleave extracellular matrix (ECM) proteins. They are also involved in the degradation of cell surface components and regulate multiple cellular processes, cell to cell interactions, cell proliferation, and cell signaling pathways. MMPs function in close interaction with the endogenous tissue inhibitors of matrix metalloproteinases (TIMPs), both of which regulate cell turnover, modulate various growth factors, and participate in the progression of tissue fibrosis and apoptosis. The multiple roles of MMPs and TIMPs are continuously elucidated in kidney development and repair, as well as in a number of kidney diseases. This chapter focuses on the current findings of the significance of MMPs and TIMPs in a wide range of kidney diseases, whether they result from kidney tissue changes, hemodynamic alterations, tubular epithelial cell apoptosis, inflammation, or fibrosis. In addition, the potential use of these endopeptidases as biomarkers of renal dysfunction and as targets for therapeutic interventions to attenuate kidney disease are also explored in this review.

• MeSH
• extracelulární matrix - proteiny MeSH
• lidé MeSH
• matrixové metaloproteinasy metabolismus   MeSH
• nemoci ledvin * MeSH
• signální transdukce MeSH
• tkáňové inhibitory metaloproteinas * metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Automated chip capillary electrophoresis was used in detection and isolation of lactoferrin and a human matrix metalloproteinase (MMP-9) as well as in investigation of interactions and cleavage of collagen with MMP-9. The method is a sensitive and simple technique superior to SDS-PAGE. It is useful in proteomic research.

• MeSH
• elektroforéza mikročipová MeSH
• elektroforéza v agarovém gelu MeSH
• financování organizované MeSH
• laktoferrin analýza   MeSH
• matrixové metaloproteinasy analýza   MeSH