Bral1 is a link protein that stabilizes the binding between lecticans and hyaluronic acid and thus maintains the extracellular matrix assembly in the CNS. Bral1 is specifically located in the white matter around the nodes of Ranvier. Recent studies suggest its function in promoting saltatory neural conduction. This article reviews the current knowledge about the structure, expression and function of this link protein.

• MeSH
• extracelulární matrix metabolismus   MeSH
• lidé MeSH
• mozek cytologie   metabolismus   MeSH
• proteiny nervové tkáně chemie   metabolismus   MeSH
• regulace genové exprese MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• proteiny nervové tkáně MeSH

Vascular surgery for atherosclerosis is confronted by the lack of a suitable bypass material. Tissue engineering strives to produce bio-artificial conduits to provide resistance to thrombosis. The objectives of our study were to culture endothelial cells (EC) on composite assemblies of extracellular matrix proteins, and to evaluate the cellular phenotype under flow. Cell-adhesive assemblies were fabricated on glass slides as combinations of collagen (Co), laminin (LM), and fibronectin (FN), resulting in three samples: Co, Co/LM, and Co/FN. Surface topography, roughness, and wettability were determined. Human saphenous vein EC were harvested from cardiac patients, cultured on the assemblies and submitted to laminar shear stress (SS) of 12 dyn/cm(2) for 40, 80, and 120 min. Cell retention was assessed and qRT-PCR of adhesion genes (VE-cadherin, vinculin, KDR, CD-31 or PECAM-1, β1-integrins) and metabolic genes (t-PA, NF-κB, eNOS and MMP-1) was performed. Quantitative immunofluorescence of VE cadherin, vinculin, KDR, and vonWillebrand factor was performed after 2 and 6 h of flow. Static samples were excluded from shearing. The cells reached confluence with similar growth curves. The cells on Co/LM and Co/FN were resistant to flow up to 120 min but minor desquamation occurred on Co corresponding with temporary downregulation of VE cadherin and vinculin-mRNA and decreased fluorescence of vinculin. The cells seeded on Co/LM initially more upregulated vinculin-mRNA and also the inflammatory factor NF-κB, and the cells plated on Co/FN changed the expression profile minimally in comparison with the static control. Fluorescence of VE cadherin and vonWillebrand factor was enhanced on Co/FN. The cells cultured on Co/LM and Co/FN increased the vinculin fluorescence and expressed more VE cadherin and KDR-mRNA than the cells on Co. The cells plated on Co/FN upregulated the mRNA of VE cadherin, CD-31, and MMP 1 to a greater extent than the cells on Co/LM and they enhanced the fluorescence of VE cadherin, KDR, and vonWillebrand factor. Some of these changes sustained up to 6 h of flow, as confirmed by immunofluorescence. Combined matrices Co/LM and Co/FN seem to be more suitable for EC seeding and retention under flow. Moreover, Co/FN matrix promoted slightly more favorable cellular phenotype than Co/LM under SS of 2-6 h.

• MeSH
• buněčná adheze účinky léků   MeSH
• časové faktory MeSH
• endoteliální buňky účinky léků   metabolismus   MeSH
• extracelulární matrix - proteiny farmakologie   MeSH
• fluorescenční protilátková technika MeSH
• krysa rodu Rattus MeSH
• lidé MeSH
• mechanický stres * MeSH
• myši MeSH
• pevnost ve smyku * MeSH
• povrchová plasmonová rezonance MeSH
• proliferace buněk účinky léků   MeSH
• regulace genové exprese účinky léků   MeSH
• smáčivost MeSH
• stanovení celkové genové exprese MeSH
• vena saphena cytologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• extracelulární matrix - proteiny MeSH

Paxillin (PXN) is a focal adhesion protein that has been implicated in signal transduction from the extracellular matrix. Recently, it has been shown to shuttle between the cytoplasm and the nucleus. When inside the nucleus, paxillin promotes cell proliferation. Here, we introduce paxillin as a transcriptional regulator of IGF2 and H19 genes. It does not affect the allelic expression of the two genes; rather, it regulates long-range chromosomal interactions between the IGF2 or H19 promoter and a shared distal enhancer on an active allele. Specifically, paxillin stimulates the interaction between the enhancer and the IGF2 promoter, thus activating IGF2 gene transcription, whereas it restrains the interaction between the enhancer and the H19 promoter, downregulating the H19 gene. We found that paxillin interacts with cohesin and the mediator complex, which have been shown to mediate long-range chromosomal looping. We propose that these interactions occur at the IGF2 and H19 gene cluster and are involved in the formation of loops between the IGF2 and H19 promoters and the enhancer, and thus the expression of the corresponding genes. These observations contribute to a mechanistic explanation of the role of paxillin in proliferation and fetal development.

• Klíčová slova
• Cohesin, Enhancer, H19, IGF2, Imprinting, Paxillin,
• MeSH
• buňky Hep G2 MeSH
• chromozomální proteiny, nehistonové genetika   MeSH
• extracelulární matrix genetika   MeSH
• fokální adheze genetika   MeSH
• genomový imprinting genetika   MeSH
• insulinu podobný růstový faktor II biosyntéza   genetika   MeSH
• koheziny MeSH
• lidé MeSH
• metylace DNA genetika   MeSH
• paxilin aplikace a dávkování   MeSH
• proliferace buněk účinky léků   genetika   MeSH
• promotorové oblasti (genetika) MeSH
• proteiny buněčného cyklu genetika   MeSH
• RNA dlouhá nekódující biosyntéza   genetika   MeSH
• signální transdukce účinky léků   MeSH
• vývoj plodu genetika   MeSH
• vývojová regulace genové exprese MeSH
• zesilovače transkripce MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• chromozomální proteiny, nehistonové MeSH
• H19 long non-coding RNA MeSH Prohlížeč
• IGF2 protein, human MeSH Prohlížeč
• insulinu podobný růstový faktor II MeSH
• paxilin MeSH
• proteiny buněčného cyklu MeSH
• RNA dlouhá nekódující MeSH

Matrix metalloproteinases (MMPs), also known as matrixins, belong to a group of zinc-dependent proteins, which are thought to play a central role in the breakdown of extracellular matrix. Collagen, elastin, gelatin and casein are major components cleaved by MMPs. The breakdown of these components is essential for many physiological processes such as embryonic development, morphogenesis, reproduction, and tissue resorption and remodelling. MMPs also participate in pathological processes such as arthritis, cancer, cardiovascular and neurological diseases. This review summarizes current knowledge regarding these proteins, their participation in physiological and pathophysiological roles, their involvement in activation and inhibition, and their interactions with other metal-binding proteins including metallothioneins.

• MeSH
• cystein metabolismus   MeSH
• extracelulární matrix metabolismus   MeSH
• inhibitory matrixových metaloproteinas MeSH
• kardiovaskulární nemoci farmakoterapie   enzymologie   patofyziologie   MeSH
• lidé MeSH
• matrixové metaloproteinasy chemie   genetika   metabolismus   MeSH
• nádory farmakoterapie   enzymologie   patofyziologie   MeSH
• regulace genové exprese enzymů MeSH
• sloučeniny zinku chemie   metabolismus   farmakologie   MeSH
• substrátová specifita MeSH
• tkáňové inhibitory metaloproteinas metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• cystein MeSH
• inhibitory matrixových metaloproteinas MeSH
• matrixové metaloproteinasy MeSH
• sloučeniny zinku MeSH
• tkáňové inhibitory metaloproteinas MeSH

Although colonies from Saccharomyces cerevisiae laboratory strains are smooth, those isolated from nature exhibit a structured fluffy pattern. Environmental scanning electron microscopy shows that the cells within wild fluffy colonies are connected by extracellular matrix (ECM) material. This material contains a protein of about 200 kDa unrelated to the flocculins, proteins involved in cell-cell adhesion in liquid media. The matrix material binds to concanavalin A. Within a few passages on rich agar medium, the wild strains switch from the fluffy to the smooth colony morphology. This domestication is accompanied by loss of the ECM and by extensive changes in gene expression as detected by DNA microarrays. The expression of about 320 genes was changed in smooth colonies. The major changes comprise carbohydrate metabolism, cell wall, water channels, Ty-transposons and subtelomeric genes, iron homeostasis, vitamin metabolism and cell cycle and polarity. The growth in fluffy colonies may represent a metabolic strategy for survival of yeast under unfavourable conditions that is switched off under felicitous laboratory conditions.

• MeSH
• extracelulární matrix metabolismus   MeSH
• genetická transkripce * MeSH
• kultivační média MeSH
• laboratoře MeSH
• mikrobiologie životního prostředí MeSH
• regulace genové exprese u hub * MeSH
• Saccharomyces cerevisiae - proteiny genetika   metabolismus   MeSH
• Saccharomyces cerevisiae genetika   růst a vývoj   metabolismus   ultrastruktura   MeSH
• sekvenční analýza hybridizací s uspořádaným souborem oligonukleotidů MeSH
• stanovení celkové genové exprese MeSH
• výpočetní biologie MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• kultivační média MeSH
• Saccharomyces cerevisiae - proteiny MeSH

During development, tooth germs undergo various morphological changes resulting from interactions between the oral epithelium and ectomesenchyme. These processes are influenced by the extracellular matrix, the composition of which, along with cell adhesion and signaling, is regulated by metalloproteinases. Notably, these include matrix metalloproteinases (MMPs), a disintegrin and metalloproteinases (ADAMs), and a disintegrin and metalloproteinases with thrombospondin motifs (ADAMTSs). Our analysis of previously published scRNAseq datasets highlight that these metalloproteinases show dynamic expression patterns during tooth development, with expression in a wide range of cell types, suggesting multiple roles in tooth morphogenesis. To investigate this, Marimastat, a broad-spectrum inhibitor of MMPs, ADAMs, and ADAMTSs, was applied to ex vivo cultures of mouse molar tooth germs. The treated samples exhibited significant changes in tooth germ size and morphology, including an overall reduction in size and an inversion of the typical bell shape. The cervical loop failed to extend, and the central area of the inner enamel epithelium protruded. Marimastat treatment also disrupted proliferation, cell polarization, and organization compared with control tooth germs. In addition, a decrease in laminin expression was observed, leading to a disruption in continuity of the basement membrane at the epithelial-mesenchymal junction. Elevated hypoxia-inducible factor 1-alpha gene (Hif-1α) expression correlated with a disruption to blood vessel development around the tooth germs. These results reveal the crucial role of metalloproteinases in tooth growth, shape, cervical loop elongation, and the regulation of blood vessel formation during prenatal tooth development.NEW & NOTEWORTHY Inhibition of metalloproteinases during tooth development had a wide-ranging impact on molar growth affecting proliferation, cell migration, and vascularization, highlighting the diverse role of these proteins in controlling development.

• Klíčová slova
• blood vessels, cervical loop, extracellular matrix, metalloproteinases, tooth germ morphogenesis,
• MeSH
• faktor 1 indukovatelný hypoxií - podjednotka alfa metabolismus   genetika   MeSH
• inhibitory matrixových metaloproteinas farmakologie   MeSH
• kyseliny hydroxamové farmakologie   MeSH
• metaloproteasy metabolismus   genetika   MeSH
• moláry embryologie   růst a vývoj   metabolismus   enzymologie   MeSH
• morfogeneze MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• odontogeneze * MeSH
• proliferace buněk * MeSH
• vývojová regulace genové exprese MeSH
• zubní zárodek embryologie   metabolismus   enzymologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• faktor 1 indukovatelný hypoxií - podjednotka alfa MeSH
• inhibitory matrixových metaloproteinas MeSH
• kyseliny hydroxamové MeSH
• marimastat MeSH Prohlížeč
• metaloproteasy MeSH

Matrix metalloproteinases (MMPs) are proteolytic enzymes involved in tissue remodeling and wound healing. These enzymes degrade and also synthesize components of the extracellular matrix. Overexpression of MMPs results in excessive extracellular matrix degradation and tissue destruction. In the cornea, destructive processes may lead to scarring and loss of vision. In this study MMPs (types 1, 2, 7, 8, 9 and 14) were examined immunohistochemically in the normal rabbit corneal epithelium and in epithelium irradiated in vivo with similar doses of UVB or UVA radiation (UVB rays 312 nm, UVA rays 365 nm, daily dose 1.01 J/cm(2) for four days). Results show that MMPs studied revealed low expression in the normal corneal epithelium, whereas after repeated UVB irradiation the expression of MMPs was significantly increased in the corneal epithelium, in ascending order: MMP-2, MMP-9, MMP-1, and MMP-7 with MMP-8. In contrast, compared to normal corneas, repeated UVA radiation did not significantly change the expression of MMPs in the irradiated corneal epithelium. MMP-14 was expressed at very low levels in all studied corneas, whereas no significant changes were detected upon UV exposure. In conclusion, UV radiation of shorter wavelength (UVB) induced an increase in expression of all MMPs except MMP-14. It is suggested that overexpression of MMPs in the corneal epithelium contributes to the damaging effect of UVB radiation to the cornea.

• MeSH
• imunohistochemie MeSH
• králíci MeSH
• matrixové metaloproteinasy analýza   biosyntéza   MeSH
• regulace genové exprese enzymů účinky záření   MeSH
• rohovkový epitel enzymologie   účinky záření   MeSH
• ultrafialové záření * MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• matrixové metaloproteinasy MeSH

The myocardial extracellular matrix plays an important role in maintaining the structural and functional integrity of the heart and is centrally involved in post-myocardial infarction repair processes. We analysed some genetic and proteomic aspects that could play an important role in the development of myocardial infarction. Matrix metalloproteinases are enzymes that contribute strongly to the degradation of extracellular matrix components. In this study the serological levels of MMP-2 and MMP-9 were investigated using immunological testing in 34 patients with myocardial infarction and 34 matched control subjects. The serum levels of MMPs were determined by ELISA. Changes in serum levels were characterized within 24 h and after 6 months post myocardial infarction. Significantly higher levels of MMP-2 (299.47 ± 117.61 ng/ml) and MMP-9 (93.56 ± 53.74 ng/ml) were determined in patients with myocardial infarction compared to the controls, in both cases P < 0.001. MMP-9 levels decreased significantly in the 6 months after cardiac event, whereas the levels of MMP-2 were almost equal to the post-infarction ones. While comparing the results from four patients that died of cardiovascular cause within 6 months we found significantly higher MMP-2 (435.00 ± 55.83 ng/ml, P = 0.003) and MMP-9 (166.25 ± 41.07 ng/ml, P = 0.018) values. Microarray analysis was used to determine the gene expression of selected genes for MMPs and their regulators from peripheral blood. The selected genes did not show satisfactory results that could have a potential implication for diagnostics of tissue degeneration.

• MeSH
• infarkt myokardu krev   enzymologie   genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• matrixová metaloproteinasa 2 krev   MeSH
• matrixová metaloproteinasa 9 krev   MeSH
• regulace genové exprese MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři 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

BACKGROUND Paracrine factors secreted by adipose-derived stem cells can be captured, fractionated, and concentrated to produce therapeutic factor concentrate (TFC). The present study examined whether TFC effects could be enhanced by combining TFC with a biological matrix to provide sustained release of factors in the target region. MATERIAL AND METHODS Unilateral hind limb ischemia was induced in rabbits. Ischemic limbs were injected with either placebo control, TFC, micronized small intestinal submucosa tissue (SIS), or TFC absorbed to SIS. Blood flow in both limbs was assessed with laser Doppler perfusion imaging. Tissues harvested at Day 48 were assessed immunohistochemically for vessel density; in situ hybridization and quantitative real-time PCR were employed to determine miR-126 expression. RESULTS LDP ratios were significantly elevated, compared to placebo control, on day 28 in all treatment groups (p=0.0816, p=0.0543, p=0.0639, for groups 2-4, respectively) and on day 36 in the TFC group (p=0.0866). This effect correlated with capillary density in the SIS and TFC+SIS groups (p=0.0093 and p=0.0054, respectively, compared to placebo). A correlation was observed between miR-126 levels and LDP levels at 48 days in SIS and TFC+SIS groups. CONCLUSIONS A single bolus administration of TFC and SIS had early, transient effects on reperfusion and promotion of ischemia repair. The effects were not additive. We also discovered that TFC modulated miR-126 levels that were expressed in cell types other than endothelial cells. These data suggested that TFC, alone or in combination with SIS, may be a potent therapy for patients with CLI that are at risk of amputation.

• MeSH
• extracelulární matrix metabolismus   MeSH
• ischemie genetika   patologie   terapie   MeSH
• kmenové buňky cytologie   MeSH
• končetiny krevní zásobení   patologie   MeSH
• králíci MeSH
• kůže patologie   MeSH
• laser doppler flowmetrie MeSH
• lidé středního věku MeSH
• lidé MeSH
• mikro RNA genetika   metabolismus   MeSH
• mikropartikule metabolismus   MeSH
• modely nemocí na zvířatech MeSH
• perfuze MeSH
• regulace genové exprese MeSH
• reperfuzní poškození patologie   terapie   MeSH
• střevní sliznice fyziologie   MeSH
• tenké střevo fyziologie   MeSH
• transplantace kmenových buněk * MeSH
• tuková tkáň cytologie   MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• mikro RNA MeSH

This study presents a toxicological evaluation of two types of carbon dots (CD), similar in size (<10 nm) but differing in surface charge. Whole-genome mRNA and miRNA expression (RNAseq), as well as gene-specific DNA methylation changes, were analyzed in human embryonic lung fibroblasts (HEL 12469) after 4 h and 24 h exposure to concentrations of 10 and 50 µg/mL (for positive charged CD; pCD) or 10 and 100 µg/mL (for negative charged CD, nCD). The results showed a distinct response for the tested nanomaterials (NMs). The exposure to pCD induced the expression of a substantially lower number of mRNAs than those to nCD, with few commonly differentially expressed genes between the two CDs. For both CDs, the number of deregulated mRNAs increased with the dose and exposure time. The pathway analysis revealed a deregulation of processes associated with immune response, tumorigenesis and cell cycle regulation, after exposure to pCD. For nCD treatment, pathways relating to cell proliferation, apoptosis, oxidative stress, gene expression, and cycle regulation were detected. The expression of miRNAs followed a similar pattern: more pronounced changes after nCD exposure and few commonly differentially expressed miRNAs between the two CDs. For both CDs the pathway analysis based on miRNA-mRNA interactions, showed a deregulation of cancer-related pathways, immune processes and processes involved in extracellular matrix interactions. DNA methylation was not affected by exposure to any of the two CDs. In summary, although the tested CDs induced distinct responses on the level of mRNA and miRNA expression, pathway analyses revealed a potential common biological impact of both NMs independent of their surface charge.

• Klíčová slova
• DNA methylation, carbon dots, gene expression, human lung fibroblasts, surface charge,
• MeSH
• apoptóza účinky léků   genetika   MeSH
• exprese genu účinky léků   genetika   MeSH
• extracelulární matrix genetika   MeSH
• fibroblasty účinky léků   MeSH
• kultivované buňky MeSH
• lidé MeSH
• messenger RNA genetika   MeSH
• metylace DNA účinky léků   genetika   MeSH
• mikro RNA genetika   MeSH
• nádory genetika   MeSH
• oxidační stres účinky léků   genetika   MeSH
• plíce účinky léků   MeSH
• proliferace buněk účinky léků   genetika   MeSH
• signální transdukce účinky léků   genetika   MeSH
• stanovení celkové genové exprese metody   MeSH
• uhlík farmakologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• messenger RNA MeSH
• mikro RNA MeSH
• uhlík MeSH