Cholera toxin perturbs the paracellular barrier in the small intestinal epithelium of rats by affecting claudin-2 and tricellulin

Markov, Alexander G.; Vishnevskaya, O. N.; Okorokova, Larisa S.; Fedorova, Arina A.; Круглова, Н М; Рыбальченко, Оксана Владимировна; Aschenbach, Jörg R.; Amasheh, Salah

doi:10.1007/s00424-019-02294-z

Cited by 8 publications

(6 citation statements)

References 29 publications

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“…In several gastrointestinal disorders, such as IBDs or gastrointestinal carcinomas, the expression of claudin-2 is increased ( Aung et al, 2006 ; Mankertz and Schulzke, 2007 ). An increase of claudin-2 in the intestine results in a drop in TER and in increased paracellular permeability ( Ahmad et al, 2014 ; Wang et al, 2017 ; Markov et al, 2019 ). This is in accordance with our findings in the current study, as we have detected an increase of claudin-2 after 10 h incubation with TNF.…”

Section: Discussionmentioning

confidence: 99%

Barrier Perturbation in Porcine Peyer’s Patches by Tumor Necrosis Factor is Associated With a Dysregulation of Claudins

et al. 2022

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The proinflammatory cytokine tumor necrosis factor (TNF) has been described as one of the main mediators of intestinal inflammatory diseases, affecting the composition of tight junction (TJ) proteins and leading to a disruption of the epithelial barrier. An intact intestinal barrier is mandatory, because the follicle-associated epithelium of Peyer’s patches represents the first defense line of the intestinal immune system and ensures a controlled uptake of antigens from the gut lumen. In the current study, we have analyzed the detailed effects of TNF on the follicle-associated epithelium of porcine Peyer’s patches by applying the Ussing chamber technique. Epithelial tissue specimens of Peyer’s patches and the surrounding villus epithelium were mounted into conventional Ussing chambers and incubated with TNF for 10 h. The transepithelial resistance, representing epithelial barrier function of the tissue, was recorded. A reduction of transepithelial resistance was detected after 8 h in Peyer’s patch tissue specimens, whereas the villus epithelium was not significantly affected by TNF. Subsequent molecular analysis of TJ protein expression revealed a marked decrease of claudin-1 and -4, and an increase of claudin-2. In neighboring villus epithelium, no significant changes in the expression of TJ proteins could be shown. A strong increase of TNF receptor-2 (TNFR-2) could also be detected in Peyer’s patches, in agreement with the major role of this receptor in Peyer’s patches. Our findings were in accordance with changes detected by confocal laser scanning immunofluorescence microscopy. The regulation of TNF effects via myosin light chain kinase (MLCK) was analyzed in blocking experiments. Our detailed analysis is the first to show that TNF affects the barrier function of the follicle-associated epithelium of porcine Peyer’s patches but has no effects on the villus epithelium. These findings reveal not only the basic differences of epithelial barrier function between the two structures, but also the significance of Peyer’s patches as a primary mucosal immune defense.

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Section: Discussionmentioning

confidence: 99%

Barrier Perturbation in Porcine Peyer’s Patches by Tumor Necrosis Factor is Associated With a Dysregulation of Claudins

et al. 2022

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“…Previous observations suggest that mouse colon is relatively resistant to such injury as radiation compared to the jejunum [ 57 ]. Other data also demonstrated that cholera toxin differently affected claudin expression in rat colon [ 51 ] and jejunum [ 58 ]. In our study, the expression of claudins in rat colon was relatively resistant to chronic ouabain exposure as well as to LPS- or HS-induced injury in a combination with ouabain pre-treatment (TER measurements).…”

Section: Discussionmentioning

confidence: 99%

Circulating Ouabain Modulates Expression of Claudins in Rat Intestine and Cerebral Blood Vessels

Markov

Fedorova

Кравцова

et al. 2020

IJMS

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The ability of exogenous low ouabain concentrations to affect claudin expression and therefore epithelial barrier properties was demonstrated previously in cultured cell studies. We hypothesized that chronic elevation of circulating ouabain in vivo can affect the expression of claudins and tight junction permeability in different tissues. We tested this hypothesis in rats intraperitoneally injected with ouabain (1 μg/kg) for 4 days. Rat jejunum, colon and brain frontal lobes, which are variable in the expressed claudins and tight junction permeability, were examined. Moreover, the porcine jejunum cell line IPEC-J2 was studied. In IPEC-J2-cells, ouabain (10 nM, 19 days of incubation) stimulated epithelial barrier formation, increased transepithelial resistance and the level of cSrc-kinase activation by phosphorylation, accompanied with an increased expression of claudin-1, -5 and down-regulation of claudin-12; the expression of claudin-3, -4, -8 and tricellulin was not changed. In the jejunum, chronic ouabain increased the expression of claudin-1, -3 and -5 without an effect on claudin-2 and -4 expression. In the colon, only down-regulation of claudin-3 was observed. Chronic ouabain protected the intestine transepithelial resistance against functional injury induced by lipopolysaccharide treatment or by modeled acute microgravity; this regulation was most pronounced in the jejunum. Сlaudin-1 was also up-regulated in cerebral blood vessels. This was associated with reduction of claudin-3 expression while the expression of claudin-5 and occludin was not affected. Altogether, our results confirm that circulating ouabain can functionally and tissue-specifically affect barrier properties of epithelial and endothelial tissues via Na,K-ATPase-mediated modulation of claudins expression.

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“…Intestinal segments were fixed in 4% paraformaldehyde and embedded in paraffin. Then, 5 μ m slides were made and stained with anti-claudin-2 and anti-occludin according to a previous report [ 21 ]. Tissues were incubated with primary antibodies for 60 min and then incubated with diluted 1 : 500 Alexa Fluor IgG for 45 min in blocking solution.…”

Section: Methodsmentioning

confidence: 99%

Role of Autophagy Inducers and Inhibitors in Intestinal Barrier Injury Induced by Intestinal Ischemia–Reperfusion (I/R)

Zhang

et al. 2022

Journal of Immunology Research

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Objectives. Intestinal epithelial barrier function is an important mechanical barrier to maintain intestinal homeostasis and resist the invasion of intestinal pathogens and microorganisms. However, intestinal epithelial barrier function is vulnerable to damage under intestinal ischemia–reperfusion (I/R) injury. Under a category of pathophysiological conditions, including I/R, autophagy plays a crucial role. This study is aimed at discussing the role of autophagy inhibitors and activators in intestinal epithelial barrier function after intestinal I/R by changing autophagy levels. Methods. Mice with intestinal IR underwent 45 minutes of surgery for superior mesenteric artery occlusion. The autophagy inhibitor 3-MA and the autophagy inducer rapamycin (RAP) were used to change the level of autophagy, and then, the expressions of tight junction proteins and intestinal barrier function were detected. Results. The results showed that the autophagy inhibitor 3-MA aggravated intestinal epithelial barrier dysfunction, while the autophagy inducer RAP attenuated intestinal epithelial barrier dysfunction. In addition, promoting autophagy may promote occludin expression by inhibiting claudin-2 expression. Conclusion. Upregulation of autophagy levels by autophagy inducers can enhance intestinal epithelial barrier function after intestinal I/R.

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Cholera toxin perturbs the paracellular barrier in the small intestinal epithelium of rats by affecting claudin-2 and tricellulin

Cited by 8 publications

References 29 publications

Barrier Perturbation in Porcine Peyer’s Patches by Tumor Necrosis Factor is Associated With a Dysregulation of Claudins

Barrier Perturbation in Porcine Peyer’s Patches by Tumor Necrosis Factor is Associated With a Dysregulation of Claudins

Circulating Ouabain Modulates Expression of Claudins in Rat Intestine and Cerebral Blood Vessels

Role of Autophagy Inducers and Inhibitors in Intestinal Barrier Injury Induced by Intestinal Ischemia–Reperfusion (I/R)

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