Intestinal Epithelium Dotaz Zobrazit nápovědu
Morphological differentiation of the intestinal epithelium in the laboratory rat occurs between the 16th and 21st day of prenatal development. The pseudostratified epithelium is rebuilt into simple epithelium of the future lining. A characteristic sign of this rebuilding is formation of primitive folds, villi and intraepithelial vacuoles corresponding in submicroscopic picture with a secondary luminization. On the tips of folds and villi groups of cells released from the epithelium are observed. In these cells expression of activated caspase-3 confirms the presence of apoptosis in the process of cell death during epithelium rebuilding.
- MeSH
- apoptóza MeSH
- epitel embryologie ultrastruktura MeSH
- kolon cytologie embryologie ultrastruktura MeSH
- krysa rodu Rattus MeSH
- střevní sliznice cytologie embryologie ultrastruktura MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The ability of some pathogenic strains of E. coli to adhere to the intestinal epithelium significantly enhances their effectivity. This adhesion of particular pigs' strains is mediated by specific pili possessing the K 88 antigen found on the outer membrane of the bacterial cell. In in vitro experiments with isolated piglets' enterocytes, a considerable adherence of the E. coli K 88+ strain was found when compared with the same bacterial strain but lacking this plasmid-directed antigen. Comparable results were obtained in in vivo experiments with ligated intestinal loops as well as with monoassociated piglets. Furthermore, the adherence ability is most pronounced at the early postnatal period and is negligible in adult pigs.
The first step in the development of human colorectal cancer is aberrant activation of the Wnt signaling pathway. Wnt signaling hyperactivation is predominantly caused by loss-of-function mutations in the adenomatous polyposis coli (APC) gene that encodes the pathway negative regulator. In order to identify genes affected by the Apc loss, we performed expression profiling of intestinal epithelium isolated from mice harboring a conditional Apc allele. The gene encoding transcriptional factor msh homeobox 1 (Msx1) displayed robust upregulation upon Apc inactivation. Histological analysis of the Apc-deficient epithelium revealed that in the small intestine, the Msx1 protein was localized exclusively in ectopic crypts, i.e., in pockets of proliferating cells abnormally positioned on the villi. Ablation of the Msx1 gene leads to the disappearance of ectopic crypts and loss of differentiated cells. Moreover, tumors arising from Msx1-deficient cells display altered morphology reminiscent of villous adenomas. In human tumor specimens, MSX1 displayed significantly increased expression in colonic neoplasia with a descending tendency during the lesion progression towards colorectal carcinoma. In summary, the results indicate that Msx1 represents a novel marker of intestinal tumorigenesis. In addition, we described the previously unknown relationship between the Msx1-dependent formation of ectopic crypts and cell differentiation.
- MeSH
- beta-katenin metabolismus MeSH
- buněčná diferenciace MeSH
- kolorektální nádory genetika patologie MeSH
- lidé MeSH
- myši knockoutované MeSH
- nádory tračníku genetika patologie MeSH
- protein familiární adenomatózní polypózy genetika metabolismus MeSH
- regulace genové exprese u nádorů MeSH
- signální dráha Wnt MeSH
- stanovení celkové genové exprese MeSH
- střevní sliznice metabolismus patologie MeSH
- tenké střevo patologie MeSH
- transkripční faktor MSX1 genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- adenomatous polyposis coli protein, mouse MeSH Prohlížeč
- APC protein, human MeSH Prohlížeč
- beta-katenin MeSH
- MSX1 protein, human MeSH Prohlížeč
- Msx1 protein, mouse MeSH Prohlížeč
- protein familiární adenomatózní polypózy MeSH
- transkripční faktor MSX1 MeSH
Puwainaphycins (PUW) and minutissamides (MIN) are cyanobacterial lipopeptides found in various cyanobacterial species. The first possible target of human exposure to them is intestinal epithelium but effect of PUW/MIN on enterocytes is not known at all. Using differentiated Caco-2 cells, PUW F was found to be cytotoxic from 5 µM concentration based on lactate dehydrogenase release assay and total protein concentration. However, it is also able to induce production of interleukin 8 in non-cytotoxic concentrations 1 and 2.5 µM detected by ELISA. Effects of MIN A and C were similar but less pronounced compared to PUW F. On the other hand, MIN D was the least toxic compound with no significant pro-inflammatory effects. Surprisingly, pro-inflammatory activation of the cells by PUW F and MIN C resulted in an increase in tight junction (TJ) protein claudin 4 expression determined by western blot analysis and confirmed by confocal microscopy. Furthermore, decrease in expression of zonula occludens 3, another TJ protein, was observed after the exposure to PUW F. Taken together, these cytotoxic lipopeptides, especially PUW F, are to be studied more deeply due to their capability to activate and/or deregulate human enterocytes in low concentrations.
- Klíčová slova
- Cytotoxicity, Inflammation, Intestinal epithelium, Minutissamides, Puwainaphycins, Tight junction,
- MeSH
- Caco-2 buňky MeSH
- lidé MeSH
- lipopeptidy * MeSH
- sinice * MeSH
- střevní sliznice MeSH
- těsný spoj MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- lipopeptidy * MeSH
The diagnosis and assessment of the severity of intestinal mucosal damage in cancer patients treated with cytotoxic drugs still rely on anamnestic data. There is cumulative evidence that measurement of intestinal permeability may represent a sensitive indicator of intestinal damage by cytotoxic agents. The intestinal permeability testing is based on differential permeability of tight junctions along the crypt-villus axis to nonmetabolized sugars. Cytotoxic drugs induce flattening of villi, leading to increased exposure of luminal contents to crypts and increased disaccharide absorption. An increased disaccharide/monosaccharide ratio and decreased xylose absorption have been described in patients treated with different cytotoxic drugs across a spectrum of malignant tumors that correlated with clinical manifestations, and were used to monitor the effect of therapeutic interventions.
- MeSH
- lidé MeSH
- mukozitida chemicky indukované diagnóza MeSH
- nádory komplikace farmakoterapie MeSH
- nemoci střev chemicky indukované diagnóza MeSH
- permeabilita MeSH
- protinádorové látky škodlivé účinky MeSH
- střevní sliznice účinky léků imunologie metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- protinádorové látky MeSH
BACKGROUND: A number of recent studies have shown that the intestinal microbiome, part of the brain-gut axis, is implicated in the pathophysiology of multiple sclerosis. An essential part of this axis, is the intestinal barrier and gastrointestinal disorders with intestinal barrier dysregulation appear to be linked to CNS demyelination, and hence involved in the etiopathogenesis of multiple sclerosis (MS). OBJECTIVE: The aim of this study was to evaluate the integrity of the intestinal barrier in patients with clinically definite multiple sclerosis (CDMS) and clinically isolated syndrome (CIS) using two serum biomarkers, claudin-3 (CLDN3), a component of tight epithelial junctions, and intestinal fatty acid binding protein (I-FABP), a cytosolic protein in enterocytes. METHODS: Serum levels of CLDN3 in 37 MS patients and 22 controls, and serum levels of I-FABP in 46 MS patients and 51 controls were measured using commercial ELISA kits. Complete laboratory tests excluded the presence of gluten-related disorders in all subjects. Thirty MS patients received either disease-modifying drugs (DMD), immunosuppression (IS) or corticosteroid treatment. RESULTS: CLDN3 levels were only significantly higher in the MS patients treated with DMD or IS compared to the control group (P=0.006). There were no differences in I-FABP serum levels between the groups. Serum CLDN3 levels did not correlate with serum I-FABP levels in CDMS, in CIS patients or controls. CONCLUSIONS: In multiple sclerosis patients, the intestinal epithelium may be impaired with increased permeability, but without significant enterocyte damage characterized by intracellular protein leakage. Based on our data, CLDN3 serum levels appear to assess intestinal dysfunction in MS patients but mainly in treated ones.
- Klíčová slova
- I-FABP, claudin-3, clinically isolated syndrome, intestinal permeability, multiple sclerosis,
- MeSH
- biologické markery krev MeSH
- claudin-3 * krev MeSH
- dospělí MeSH
- funkce střevní bariéry MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- permeabilita MeSH
- proteiny vázající mastné kyseliny * krev MeSH
- roztroušená skleróza * patofyziologie krev farmakoterapie MeSH
- střevní sliznice * metabolismus patofyziologie MeSH
- studie případů a kontrol MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- biologické markery MeSH
- claudin-3 * MeSH
- CLDN3 protein, human MeSH Prohlížeč
- proteiny vázající mastné kyseliny * MeSH
Freeze-fracture replicas of the plasma membrane and tight junctions (Tj) of intestinal epithelial cells were studied in Tilapia nilotica fish exposed to the pyrethroid insecticide, neopybuthrin. Exposing fishes to different repeated concentrations of 1/2 LC50 of neopybuthrin caused a significant decrease in the population density of IMPs in P- and E-faces. Tight junctions were also affected by neopybuthrin treatment. They appeared fragmented and discontinued, and their strands were fewer in number as compared with controls. Since the structure and number of Tj are major determinants of epithelial permeability, it is postulated that neopybuthrin treatment may affect the intestinal permeability of T. nilotica.
- MeSH
- epitel účinky léků ultrastruktura MeSH
- insekticidy farmakologie MeSH
- mrazové lámání MeSH
- pyrethriny farmakologie MeSH
- střevní sliznice účinky léků ultrastruktura MeSH
- Tilapia * MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- insekticidy MeSH
- neopybuthrin MeSH Prohlížeč
- pyrethriny MeSH
Intestinal milieu disorders are strongly related to the occurrence of inflammatory bowel diseases (IBDs), which results from mucosa destruction, epithelium disruption, and tight junction (TJ) proteins loss. Excess of H2 S in the intestinal milieu produced by the sulfate-reducing bacteria metabolism contributes to development of IBDs via epithelial barrier breakdown. Conventional interventions, such as surgery and anti-inflammatory medications, are considered not completely effective because of frequent recurrence and other complications. Herein, a novel oral delivery system, a hydroxypropyl methylcellulose acetate succinate (HPMCAS)-based polymer-coated Zr-based metal-organic framework (UiO-66) with a Cux -rhodamine B (CR) probe (hereinafter referred to as HUR), is produced via a co-flow microfluidic approach with the ability to reduce H2 S levels, thus restoring the intestinal lumen milieu. HPMCAS serves as an enteric coating that exposes UiO-66@CR at the pH of the intestine but not the acidic pH of the stomach. The synthesized HUR exhibits notable therapeutic efficacy, including mucosa recovery, epithelium integrity restoration, and TJ proteins upregulation via H2 S scavenging to protect against intestinal barrier damage and microbiome dysbiosis. Thus, HUR is verified to be a promising theranostic platform able to decrease the H2 S content for intestinal milieu disorder treatment. The presented study therefore opens the door for further exploitation for IBDs therapy.
- Klíčová slova
- Zr metal-organic frameworks, hydrogen sulfide scavenging, inflammatory bowel disease, intestinal milieu restoration, microfluidic technology,
- MeSH
- mikrofluidika MeSH
- porézní koordinační polymery * metabolismus MeSH
- střeva MeSH
- střevní sliznice metabolismus MeSH
- sulfan chemie MeSH
- těsný spoj MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- porézní koordinační polymery * MeSH
- sulfan MeSH
- UiO-66 MeSH Prohlížeč
The midgut epithelium of two centipedes, Lithobius forficatus and Scolopendra cingulata, is composed of digestive, secretory and regenerative cells. In L. forficatus, the autophagy occurred only in the cytoplasm of the digestive cells as a sporadic process, while in S. cingulata, it occurred intensively in the digestive, secretory and regenerative cells of the midgut epithelium. In both of the species that were analyzed, this process proceeded in a continuous manner and did not depend on the day/night cycle. Ultrastructural analysis showed that the autophagosomes and autolysosomes were located mainly in the apical and perinuclear cytoplasm of the digestive cells in L. forficatus. However, in S. cingulata, the entire cytoplasm was filled with autophagosomes and autolysosomes. Initially the membranes of phagophores surround organelles during autophagosome formation. Autolysosomes result from the fusion of autophagosomes and lysosomes. Residual bodies which are the last stage of autophagy were released into the midgut lumen due to necrosis. Autophagy in the midgut epithelia that were analyzed was confirmed using acid phosphatase and mono-dansyl-cadaverine stainings.
- Klíčová slova
- Autophagy, Centipede, Digestive cells, Midgut epithelium, Ultrastructure,
- MeSH
- autofagie * MeSH
- cirkadiánní rytmus * MeSH
- členovci cytologie fyziologie MeSH
- cytoplazma ultrastruktura MeSH
- epitelové buňky fyziologie ultrastruktura MeSH
- fagozomy ultrastruktura MeSH
- fotoperioda * MeSH
- gastrointestinální trakt fyziologie MeSH
- lyzozomy ultrastruktura MeSH
- střevní sliznice fyziologie MeSH
- transmisní elektronová mikroskopie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The gastrointestinal tract epithelium plays an important role not only in digestion and absorption of nutrients, but also in antigen and pathogen signal translocation toward the gut associated lymphoid tissue. Malnutrition in various degrees is recognized as the most common cause of the immune system dysfunction. Research done in the past several years has revealed that dietary nucleotides (dNT) represent an essential compound of nutrition because of their importance in metabolic pathways, energetic processes and nucleic acid synthesis during tissue renewal. Much evidence accumulated suggests that dNT are essential for the growth and maturation of the gut epithelia. In previous experiments we have documented immunoregulative properties of dNT-containing extracts. In this study Balb/c female mice were fed (1) standard diet, (2) dNT-supplemented diet, and (3) dNT-supplemented water for 4 weeks. The supplement in dose of 100 mg/kg/l comprised original extract (Imuregen, Uniregen Ltd., Náchod, Czech Republic). Samples of terminal ileum in each dietary group were removed for histological examination. The length of villi was evaluated by computer morphometry. The highest growth of intestinal villi was observed in group administered dNT-supplemented water. We have found no pathological changes of intestinal epithelium in any experimental group.
- MeSH
- enterocyty cytologie účinky léků MeSH
- ileum cytologie účinky léků MeSH
- myši inbrední BALB C MeSH
- myši MeSH
- nukleotidy aplikace a dávkování farmakologie MeSH
- pohárkové buňky cytologie účinky léků MeSH
- potravní doplňky * MeSH
- regenerace MeSH
- střevní sliznice cytologie účinky léků MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- nukleotidy MeSH