Upon inflammation, monocyte-derived macrophages (MΦ) infiltrate blood vessels to regulate several processes involved in vascular pathophysiology. However, little is known about the mediators involved. Macrophage polarization is crucial for a fast and efficient initial response (GM-MΦ) and a good resolution (M-MΦ) of the inflammatory process. The functional activity of polarized MΦ is exerted mainly through their secretome, which can target other cell types, including endothelial cells. Endoglin (CD105) is a cell surface receptor expressed by endothelial cells and MΦ that is markedly upregulated in inflammation and critically involved in angiogenesis. In addition, a soluble form of endoglin with anti-angiogenic activity has been described in inflammation-associated pathologies. The aim of this work was to identify components of the MΦ secretome involved in the shedding of soluble endoglin. We find that the GM-MΦ secretome contains metalloprotease 12 (MMP-12), a GM-MΦ specific marker that may account for the anti-angiogenic activity of the GM-MΦ secretome. Cell surface endoglin is present in both GM-MΦ and M-MΦ, but soluble endoglin is only detected in GM-MΦ culture supernatants. Moreover, MMP-12 is responsible for the shedding of soluble endoglin in vitro and in vivo by targeting membrane-bound endoglin in both MΦ and endothelial cells. These data demonstrate a direct correlation between GM-MΦ polarization, MMP-12, and soluble endoglin expression and function. By targeting endothelial cells, MMP-12 may represent a novel mediator involved in vascular homeostasis.

• Klíčová slova
• MMP-12, endoglin, endothelial cells, inflammation, macrophages, monocytes,
• MeSH
• biologické modely MeSH
• endoglin genetika   metabolismus   MeSH
• endoteliální buňky metabolismus   MeSH
• exprese genu MeSH
• faktor stimulující granulocyto-makrofágové kolonie metabolismus   MeSH
• faktor stimulující kolonie makrofágů metabolismus   MeSH
• kultivované buňky MeSH
• lidé MeSH
• makrofágy imunologie   metabolismus   MeSH
• matrixová metaloproteinasa 12 metabolismus   MeSH
• mediátory zánětu metabolismus   MeSH
• modely nemocí na zvířatech MeSH
• myši MeSH
• náchylnost k nemoci MeSH
• zánět etiologie   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• endoglin MeSH
• faktor stimulující granulocyto-makrofágové kolonie MeSH
• faktor stimulující kolonie makrofágů MeSH
• matrixová metaloproteinasa 12 MeSH
• mediátory zánětu MeSH

• MeSH
• bronchiální astma * farmakoterapie   MeSH
• lidé MeSH
• matrixová metaloproteinasa 12 * MeSH
• myši MeSH
• plíce MeSH
• sloučeniny síry MeSH
• tkáňový inhibitor metaloproteinasy 1 MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• dopisy MeSH
• práce podpořená grantem MeSH
• Názvy látek
• FP-025 MeSH Prohlížeč
• matrixová metaloproteinasa 12 * MeSH
• sloučeniny síry MeSH
• tkáňový inhibitor metaloproteinasy 1 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
• Názvy látek
• matrixové metaloproteinasy MeSH
• tkáňový inhibitor metaloproteinasy 2 MeSH

PURPOSE OF REVIEW: Matrix metalloproteinases (MMPs) are a family of over 20 zinc-dependent proteases with different biological and pathological activities, and many have been implicated in several diseases. Although nonselective MMP inhibitors are known to induce serious side-effects, targeting individual MMPs may offer a safer therapeutic potential for several diseases. Hence, we provide a concise overview on MMP-12, given its association with pulmonary diseases, including asthma, chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis, and other progressive pulmonary fibrosis (PPF), which may also occur in coronavirus disease 2019. RECENT FINDINGS: In asthma, COPD, and PPF, increased MMP-12 levels have been associated with inflammation and/or structural changes within the lungs and negatively correlated with functional parameters. Increased pulmonary MMP-12 levels and MMP-12 gene expression have been related to disease severity in asthma and COPD. Targeting MMP-12 showed potential in animal models of pulmonary diseases but human data are still very scarce. SUMMARY: Although there may be a potential role of MMP-12 in asthma, COPD and PPF, several pathophysiological aspects await elucidation. Targeting MMP-12 may provide further insights into MMP-12 related mechanisms and how this translates into clinical outcomes; this warrants further research.

• MeSH
• biologické markery metabolismus   MeSH
• bronchiální astma farmakoterapie   enzymologie   etiologie   patofyziologie   MeSH
• chronická obstrukční plicní nemoc farmakoterapie   enzymologie   etiologie   patofyziologie   MeSH
• COVID-19 enzymologie   etiologie   patofyziologie   MeSH
• farmakoterapie COVID-19 MeSH
• idiopatická plicní fibróza farmakoterapie   enzymologie   etiologie   patofyziologie   MeSH
• inhibitory matrixových metaloproteinas terapeutické užití   MeSH
• lidé MeSH
• matrixová metaloproteinasa 12 metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• biologické markery MeSH
• inhibitory matrixových metaloproteinas MeSH
• matrixová metaloproteinasa 12 MeSH

The interest in stem cell research continuously increased over the last decades, becoming one of the most important trends in the 21st century medicine. Stem cell-based therapies have a potential to become a solution for a range of currently untreatable diseases, such as spinal cord injuries, type I diabetes, Parkinson's disease, heart disease, stroke, and osteoarthritis. Hence, this study, based on canine material, aims to investigate the molecular basis of adipose-derived stem cell (ASC) differentiation into chondrocytes, to serve as a transcriptomic reference for further research aiming to introduce ASC into treatment of bone and cartilage related diseases, such as osteoarthritis in veterinary medicine. Adipose tissue samples were harvested from a canine specimen subjected to a routine ovariohysterecromy procedure at an associated veterinary clinic. The material was treated for ASC isolation and chondrogenic differentiation. RNA samples were isolated at day 1 of culture, day 30 of culture in unsupplemented culture media, and day 30 of culture in chondrogenic differentiation media. The resulting RNA was analyzed using RNAseq assays, with the results validated by RT-qPCR. Between differentiated chondrocytes, early and late cultures, most up- and down-regulated genes in each comparison were selected for further analysis., there are several genes (e.g., MMP12, MPEG1, CHI3L1, and CD36) that could be identified as new markers of chondrogenesis and the influence of long-term culture conditions on ASCs. The results of the study prove the usefulness of the in vitro culture model, providing further molecular insight into the processes associated with ASC culture and differentiation. Furthermore, the knowledge obtained could be used as a molecular reference for future in vivo and clinical studies.

• Klíčová slova
• RNAseq, adipose, chondrocytes, differentiation, stem cells, transcriptomics,
• MeSH
• chondrocyty * metabolismus   MeSH
• genetické markery MeSH
• kmenové buňky MeSH
• kultivační média metabolismus   MeSH
• matrixová metaloproteinasa 12 metabolismus   MeSH
• osteoartróza * genetika   metabolismus   MeSH
• psi MeSH
• RNA metabolismus   MeSH
• tuková tkáň metabolismus   MeSH
• zvířata MeSH
• Check Tag
• psi MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH
• Názvy látek
• genetické markery MeSH
• kultivační média MeSH
• matrixová metaloproteinasa 12 MeSH
• RNA MeSH

Caspase-12 is a molecule whose functions are still not well understood. Although its expression has been found in various tissues, specific roles have been described in only a few cases. These include the effect of caspase-12 on murine bone cell differentiation during craniofacial development. This work focused on the development of the limbs taking place through endochondral ossification, which precedes the formation of the cartilaginous growth plate. Caspase-12 was described here for the first time in growth plate chondrocytes during physiological development. Using pharmacological inhibition, caspase-12 was found to affect chondrogenesis. Limb-derived micromass cultures showed a significantly increased area of chondrogenic nodules after caspase-12 inhibition and there were changes in gene expression, the most significant of which was the reduction of Mmp9. These data point to potential new functions of caspase-12 in chondrogenesis.

• Klíčová slova
• Caspase-12, Chondrocyte, Chondrogenesis, Differentiation, Growth plate,
• MeSH
• buněčná diferenciace MeSH
• chondrocyty * MeSH
• chondrogeneze * fyziologie   MeSH
• inhibitory kaspas farmakologie   MeSH
• kaspasa 12 * metabolismus   genetika   MeSH
• kultivované buňky MeSH
• matrixová metaloproteinasa 9 metabolismus   genetika   MeSH
• myši MeSH
• růstová ploténka růst a vývoj   MeSH
• vývojová regulace genové exprese MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• inhibitory kaspas MeSH
• kaspasa 12 * MeSH
• matrixová metaloproteinasa 9 MeSH

Aderamastat (FP-025) is a small molecule, selective matrix metalloproteinase (MMP)-12 inhibitor, under development for respiratory conditions which may include chronic inflammatory airway diseases and pulmonary fibrosis. To support evaluation of the pharmacokinetic parameters of Aderamastat in humans, we developed and validated a high-performance liquid chromatography tandem mass spectrometry (LC-MS/MS) analytical method for the quantification of Aderamastat in human plasma. This assay was validated in compliance with the Food and Drug Administration (FDA) Good Laboratory Practice Regulations (GLP) and European Medicines Agency (EMA) guidelines. K2EDTA human plasma samples were spiked with internal standard, processed by liquid-liquid extraction, and analyzed using reversed-phase HPLC with Turbo Ion Spray® MS/MS detection. Separation was done using a chromatographic gradient on 5 µm C6-Phenyl 110 Å, 50*2 mm analytical column at a temperature of 35 °C. The LC-MS/MS bioanalytical method, developed by QPS Taiwan to determine the concentration of Aderamastat in K2EDTA human plasma, was successfully validated with respect to linearity, sensitivity, accuracy, precision, dilution, selectivity, hemolyzed plasma, lipemic plasma, batch size, recovery, matrix effect, and carry-over. These data indicate that the method for determination of Aderamastat concentrations in human K2EDTA plasma can be used in pharmacokinetics studies and subsequent clinical trials with Aderamastat. Authors declare that, this novel data is not published and not under consideration for publication by another journal than this journal. All data will be made available on request.

• Klíčová slova
• Aderamastat, Bioanalysis Assay, FP-025, LC-MS/MS, Matrix Metalloproteinase (MMP)-12 inhibitor, Validation,
• MeSH
• adamantan analogy a deriváty   krev   farmakokinetika   chemie   MeSH
• chromatografie kapalinová metody   MeSH
• EDTA * chemie   krev   farmakokinetika   MeSH
• kapalinová chromatografie-hmotnostní spektrometrie MeSH
• lidé MeSH
• limita detekce MeSH
• lineární modely MeSH
• reprodukovatelnost výsledků MeSH
• stabilita léku MeSH
• tandemová hmotnostní spektrometrie * metody   MeSH
• vysokoúčinná kapalinová chromatografie metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• adamantan MeSH
• EDTA * MeSH

OBJECTIVES: The rapidly changing treatment landscape in metastatic castration-resistant prostate cancer (mCRPC) calls for biomarkers to guide treatment decisions. We recently identified MMP-7 as a potential serum marker for the prediction of response and survival in mCRPC patients who received docetaxel (DOC) chemotherapy. Here, we aimed to test this finding in an independent patient cohort and in addition to explore the prognostic potential of serum MMP-7 in abiraterone (ABI) or enzalutamide (ENZA) treated patients. METHODS AND MATERIALS: MMP-7 levels were measured in 836 serum samples from 320 mCRPC patients collected before and during DOC (n = 95), ABI (n = 140), or ENZA (n = 85) treatment by using the ELISA method. Results were correlated with clinical and follow-up data. RESULTS: MMP-7 baseline levels were similar between the 3 treatment groups. In the ABI and ENZA cohorts, baseline MMP-7 levels were lower in patients with prior radical prostatectomy (P = 0.058 and P = 0.041, respectively). Baseline MMP-7 levels above the median were associated with shorter overall survival for the DOC (P = 0.001) and ENZA (P = 0.006) cohorts. Multivariable analyses in the DOC and ENZA cohorts revealed that high pretreatment MMP-7 level is an independent risk factor for patients' survival. In addition, in DOC-treated patients with high baseline MMP-7 level, marker decrease at the third DOC cycle was associated with improved survival. Patients with high baseline MMP-7 levels had better survival when treated with ABI compared to DOC or ENZA. CONCLUSIONS: We confirmed the prognostic value of pretreatment MMP-7 serum level and its changes as independent predictors of survival in DOC-treated mCRPC patients. In addition, high MMP-7 was a negative predictor in ENZA-treated but not in ABI-treated patients. These results warrant further research to confirm the predictive value of serum MMP-7 and to explore the potential mechanistic involvement of MMP-7 in DOC and ENZA resistance of mCRPC patients.

• Klíčová slova
• Abiraterone, Docetaxel, Enzalutamide, MMP-7, Prostate cancer,
• MeSH
• androsteny terapeutické užití   MeSH
• antitumorózní látky terapeutické užití   MeSH
• benzamidy terapeutické užití   MeSH
• docetaxel terapeutické užití   MeSH
• dospělí MeSH
• fenylthiohydantoin terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• matrixová metaloproteinasa 7 krev   MeSH
• míra přežití MeSH
• nádory prostaty rezistentní na kastraci krev   farmakoterapie   mortalita   MeSH
• nitrily terapeutické užití   MeSH
• prognóza MeSH
• retrospektivní studie 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
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• abiraterone MeSH Prohlížeč
• androsteny MeSH
• antitumorózní látky MeSH
• benzamidy MeSH
• docetaxel MeSH
• enzalutamide MeSH Prohlížeč
• fenylthiohydantoin MeSH
• matrixová metaloproteinasa 7 MeSH
• nitrily MeSH

BACKGROUND AND OBJECTIVE: Matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP) have been implicated in chronic obstructive pulmonary disease (COPD) pathogenesis. However, the majority of studies have focused on single MMP, and there is limited information on parallel expression of MMP and their antagonists TIMP. We, therefore, investigated the serum profile of MMP 1-3, 7-9, 12 and 13, and TIMP 1-4 in COPD patients. METHODS: Serum MMP 1-3, 7-9, 12 and 13, and TIMP 1-4 were measured in 74 COPD patients and 20 control subjects by multiple microsphere technology. RESULTS: MMP 1-3 and MMP 7-9 were elevated in COPD patients compared with control subjects (P= 0.001-0.043). The increased concentrations of MMP 1, 8 and 9 paralleled GOLD stage (P= 0.002-0.007). TIMP 1 and 4 concentrations were elevated in COPD (P < 0.001). MMP 1, 8 and 9, and TIMP 1 and 4 serum levels in COPD non-smokers were higher than in control non-smokers (P = 0.002-0.025). MMP 12 and 13 levels were undetectable in our serum samples. CONCLUSIONS: This study provides further evidence for increased MMP 1, 7-9, and TIMP 1 serum levels in COPD, and demonstrates for the first time serum elevation of MMP 2 and 3, and TIMP 4. The finding that circulating TIMP 4 levels are increased in COPD and the observed relationship between serum levels of MMP 1, 8 and 9, and GOLD stage requires verification in an expanded patient cohort.

• MeSH
• chronická obstrukční plicní nemoc krev   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• matrixová metaloproteinasa 1 krev   MeSH
• matrixová metaloproteinasa 2 krev   MeSH
• matrixová metaloproteinasa 3 krev   MeSH
• matrixová metaloproteinasa 7 krev   MeSH
• matrixová metaloproteinasa 8 krev   MeSH
• matrixová metaloproteinasa 9 krev   MeSH
• matrixové metaloproteinasy krev   MeSH
• senioři MeSH
• stupeň závažnosti nemoci MeSH
• tkáňové inhibitory metaloproteinas krev   MeSH
• tkáňový inhibitor metaloproteinasy 1 krev   MeSH
• tkáňový inhibitor metaloproteinasy 4 MeSH
• upregulace MeSH
• Check Tag
• dospělí MeSH
• 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
• matrixová metaloproteinasa 1 MeSH
• matrixová metaloproteinasa 2 MeSH
• matrixová metaloproteinasa 3 MeSH
• matrixová metaloproteinasa 7 MeSH
• matrixová metaloproteinasa 8 MeSH
• matrixová metaloproteinasa 9 MeSH
• matrixové metaloproteinasy MeSH
• tkáňové inhibitory metaloproteinas MeSH
• tkáňový inhibitor metaloproteinasy 1 MeSH

OBJECTIVE: To examine the expression pattern of some novel matrix metalloproteinases (MMPs) in cycling endometrium. DESIGN: Experimental study. SETTING: Department of Obstetrics and Gynecology of the Palacky University Medical School and University Hospital, Olomouc, Czech Republic, Department of Obstetrics and Gynecology, University Hospital, Lund, Sweden. METHODS: We studied MMP-12, -16, -17, -19 and -26 mRNA in 39 normal endometrial samples obtained across the menstrual cycle. Based on histological examination, all specimens were classified according to an ideal 28 day menstrual cycle as early (n=8), mid (n=6) and late (n=7) proliferative phase, early (n=4), mid (n=4) and late (n=8) secretory phase and menstrual (n=3) phase. Cycle variation was examined in frozen samples using in situ hybridization. RESULTS: Three distinct pattern of MMP mRNA expression were detected in cycling endometrium. MMP-12 was expressed predominantly in perimenstrual period, MMP-16, -17 and 19 were expressed throughout the cycle and MMP-26 was found to be maximal in periovulatory period. CONCLUSION: Different endometrial expression patterns of novel MMPs during menstrual cycle may indicate their specific roles for menstruation, endometrial growth and remodelling and implantation.

• MeSH
• dospělí MeSH
• endometrium enzymologie   MeSH
• hybridizace in situ MeSH
• lidé středního věku MeSH
• lidé MeSH
• matrixové metaloproteinasy metabolismus   MeSH
• menstruační cyklus metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• Názvy látek
• matrixové metaloproteinasy MeSH