scholarly journals Plectin ensures intestinal epithelial integrity and protects colon against colitis

2021 ◽  
Vol 14 (3) ◽  
pp. 691-702
Author(s):  
Alzbeta Krausova ◽  
Petra Buresova ◽  
Lenka Sarnova ◽  
Gizem Oyman-Eyrilmez ◽  
Jozef Skarda ◽  
...  
Keyword(s):  
Mechanical Stability ◽  
Intestinal Barrier ◽  
Intercellular Junctions ◽  
Protein Profiling ◽  
Cell Junctions ◽  
Intestinal Barrier Function ◽  
Intestinal Epithelial ◽  
Critical Determinant ◽  
In Vitro Feeding

AbstractPlectin, a highly versatile cytolinker protein, provides tissues with mechanical stability through the integration of intermediate filaments (IFs) with cell junctions. Here, we hypothesize that plectin-controlled cytoarchitecture is a critical determinant of the intestinal barrier function and homeostasis. Mice lacking plectin in an intestinal epithelial cell (IEC; PleΔIEC) spontaneously developed colitis characterized by extensive detachment of IECs from the basement membrane (BM), increased intestinal permeability, and inflammatory lesions. Moreover, plectin expression was reduced in the colons of ulcerative colitis (UC) patients and negatively correlated with the severity of colitis. Mechanistically, plectin deficiency in IECs led to aberrant keratin filament (KF) network organization and the formation of dysfunctional hemidesmosomes (HDs) and intercellular junctions. In addition, the hemidesmosomal α6β4 integrin (Itg) receptor showed attenuated association with KFs, and protein profiling revealed prominent downregulation of junctional constituents. Consistent with the effects of plectin loss in the intestinal epithelium, plectin-deficient IECs exhibited remarkably reduced mechanical stability and limited adhesion capacity in vitro. Feeding mice with a low-residue liquid diet that reduced mechanical stress and antibiotic treatment successfully mitigated epithelial damage in the PleΔIEC colon.

scholarly journals Plectin Ensures Intestinal Epithelial Integrity and Protects Colon Against Colitis

2020 ◽  
Author(s):  
Alzbeta Krausova ◽  
Petra Buresova ◽  
Lenka Sarnova ◽  
Gizem Oyman-Eyrilmez ◽  
Jozef Skarda ◽  
...  
Keyword(s):  
Mechanical Stability ◽  
Intestinal Barrier ◽  
Intercellular Junctions ◽  
Protein Profiling ◽  
Cell Junctions ◽  
Intestinal Barrier Function ◽  
Intestinal Epithelial ◽  
Critical Determinant ◽  
Keratin Filament

ABSTRACTPlectin, a highly versatile cytolinker protein, provides tissues with mechanical stability through the integration of intermediate filaments (IFs) with cell junctions. Here, we hypothesize that plectin-controlled cytoarchitecture is a critical determinant of the intestinal barrier function and homeostasis. Mice lacking plectin in intestinal epithelial cells (IEC; PleΔIEC) spontaneously developed colitis characterized by extensive detachment of IECs from the basement membrane (BM), increased intestinal permeability, and inflammatory lesions. Moreover, plectin expression was reduced in colons of ulcerative colitis (UC) patients and negatively correlated with the severity of colitis. Mechanistically, plectin deficiency in IECs led to aberrant keratin filament (KF) network organization and formation of dysfunctional hemidesmosomes (HDs) and intercellular junctions. In addition, the hemidesmosomal α6β4 integrin (Itg) receptor showed attenuated association with KFs, and protein profiling revealed prominent downregulation of junctional constituents. Consistent with effects of plectin loss in the intestinal epithelium, plectin-deficient IECs exhibited remarkably reduced mechanical stability and limited adhesion capacity in vitro. Feeding mice with a low-residue liquid diet that reduced mechanical stress and antibiotic treatment successfully mitigated epithelial damage in the PleΔIEC colon.

scholarly journals Inhibition of HtrA2 alleviated colitis by preventing necroptosis of intestinal epithelial cells

2018 ◽  
Author(s):  
Chong Zhang ◽  
Andong He ◽  
Shuai Liu ◽  
Qiaoling He ◽  
Yiqin Luo ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Rational Design ◽  
Intestinal Epithelial Cells ◽  
Intestinal Barrier ◽  
Body Weight Loss ◽  
Intestinal Barrier Function ◽  
Intestinal Epithelial ◽  
Tandem Mass Tag ◽  
Function Loss

AbstractNecroptosis of intestinal epithelial cells has been indicated to play an important role in the pathogenesis of inflammatory bowel disease (IBD). The identification of dysregulated proteins that can regulate necroptosis in dextran sulfate sodium (DSS)-induced colitis is the key to the rational design of therapeutic strategies for colitis. Through Tandem Mass Tag (TMT)-based quantitative proteomics, HtrA2 was found to be downregulated in the colon of DSS-treated mice. UCF-101, a specific serine protease inhibitor of HtrA2, significantly alleviated DSS-induced colitis as indicated by prevention of body weight loss and decreased mortality. UCF-101 decreased DSS-induced colonic inflammation, prevented intestinal barrier function loss and inhibited necroptosis of intestinal epithelial cells. In vitro, UCF-101 or silencing of HtrA2 decreased necroptosis of HT-29 and L929 cells. UCF-101 decreased phosphorylation of RIPK1 and subsequent phosphorylation of RIPK3 and MLKL during necroptosis. HtrA2 directly interacted with RIPK1 and promoted its degradation during a specific time phase of necroptosis. Our findings highlight the importance of HtrA2 in regulating colitis by modulation of necroptosis and suggest HtrA2 as an attractive target for anti-colitis treatment.

scholarly journals Exploring Effects of Chitosan Oligosaccharides on the DSS-Induced Intestinal Barrier Impairment In Vitro and In Vivo

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2199
Author(s):  
Yujie Wang ◽  
Rong Wen ◽  
Dongdong Liu ◽  
Chen Zhang ◽  
Zhuo A. Wang ◽  
...  
Keyword(s):  
Tight Junction ◽  
Structural Characteristics ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Chitosan Oligosaccharide ◽  
Intestinal Epithelial ◽  
Mucus Layer ◽  
Intestinal Mucus ◽  
Epithelial Tight Junction

Intestinal barrier dysfunction is an essential pathological change in inflammatory bowel disease (IBD). The mucus layer and the intestinal epithelial tight junction act together to maintain barrier integrity. Studies showed that chitosan oligosaccharide (COS) had a positive effect on gut health, effectively protecting the intestinal barrier in IBD. However, these studies usually focused on its impact on the intestinal epithelial tight junction. The influence of COS on the intestinal mucus layer is still poorly understood. In this study, we explored the effect of COS on intestinal mucus in vitro using human colonic mucus-secreted HT-29 cells. COS relieved DSS (dextran sulfate sodium)-induced mucus defects. Additionally, the structural characteristics of COS greatly influenced this activity. Finally, we evaluated the protective effect of COS on intestinal barrier function in mice with DSS-induced colitis. The results indicated that COS could manipulate intestinal mucus production, which likely contributed to its intestinal protective effects.

scholarly journals Caprate Modulates Intestinal Barrier Function in Porcine Peyer’s Patch Follicle-Associated Epithelium

2019 ◽  
Vol 20 (6) ◽  
pp. 1418 ◽  
Author(s):  
Judith Radloff ◽  
Valeria Cornelius ◽  
Alexander G. Markov ◽  
Salah Amasheh
Keyword(s):  
Barrier Function ◽  
Ex Vivo ◽  
Intestinal Barrier ◽  
Barrier Properties ◽  
Food Allergies ◽  
Intestinal Barrier Function ◽  
Intestinal Epithelial ◽  
Food Component ◽  
Follicle Associated Epithelium

Background: Many food components influence intestinal epithelial barrier properties and might therefore also affect susceptibility to the development of food allergies. Such allergies are triggered by increased antibody production initiated in Peyer’s patches (PP). Usually, the presentation of antigens in the lumen of the gut to the immune cells of the PP is strongly regulated by the follicle-associated epithelium (FAE) that covers the PP. As the food component caprate has been shown to impede barrier properties in villous epithelium, we hypothesized that caprate also affects the barrier function of the PP FAE, thereby possibly contributing a risk factor for the development of food allergies. Methods: In this study, we have focused on the effects of caprate on the barrier function of PP, employing in vitro and ex vivo experimental setups to investigate functional and molecular barrier properties. Incubation with caprate induced an increase of transepithelial resistance, and a marked increase of permeability for the paracellular marker fluorescein in porcine PP to 180% of control values. These effects are in accordance with changes in the expression levels of the barrier-forming tight junction proteins tricellulin and claudin-5. Conclusions: This barrier-affecting mechanism could be involved in the initial steps of a food allergy, since it might trigger unregulated contact of the gut lumen with antigens.

MicroRNA-29a mediates the impairment of intestinal epithelial integrity induced by intrauterine growth restriction in pig

2017 ◽  
Vol 312 (5) ◽  
pp. G434-G442 ◽  
Author(s):  
Yuhua Zhu ◽  
Wei Wang ◽  
Taolin Yuan ◽  
Liangliang Fu ◽  
Lian Zhou ◽  
...  
Keyword(s):  
Barrier Function ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Luciferase Reporter ◽  
Epithelial Cell Line ◽  
Regulation Mechanism ◽  
Intestinal Damage ◽  
Intestinal Epithelial ◽  
Intrauterine Growth

An important characteristic of intrauterine growth restricted (IUGR) neonate is the impaired intestinal barrier function. With the use of a pig model, this study was conducted to identify the responsible microRNA (miRNA) for the intestinal damage in IUGR neonates through comparing the miRNA profile of IUGR and normal porcine neonates and to investigate the regulation mechanism. Compared with the normal ones, we identified 83 upregulated and 76 downregulated miRNAs in the jejunum of IUGR pigs. Notably, IUGR is associated with profoundly increasesd miR-29 family and decreased expression of extracellular matrix (ECM) and tight junction (TJ) proteins in the jejunum. Furthermore, in vitro study using theporcine intestinal epithelial cell line (IPEC-1) showed that inhibition of miR-29a expression could improve the monolayer integrity by increasing cell proliferation and transepithelial resistance. Also, overexpression/inhibition of miR-29a in IPEC-1 cells can suppress/increase the expression of integrin-β1, collagen I, collagen IV, fibronectin, and claudin 1, both at transcriptional and translational levels. Subsequent luciferase reporter assay confirmed a direct interaction between miR-29a and the 3′-untranslated regions of these genes. In conclusion, this study reveals that IUGR-impaired intestinal barrier function is associated with downregulated ECM and TJ protein expression mediated by the upregulation of miR-29a. NEW & NOTEWORTHY Intrauterine growth restricted (IUGR) remains a major problem for both human health and animal production due to its association with high rates of preweaning morbidity and mortality. We have identified the abnormal expression of microRNA-29a (miR-29a) in the small intestine of IUGR neonates, as well as its targets and mechanisms. These results provide new information about biological characteristics of IUGR-affected intestinal dysfunction and can lead to the development of potentially solution for preventing and treating IUGR in the future.

scholarly journals 124 Butyric acid and derivatives: In vitro effects on barrier integrity of porcine intestinal epithelial cells quantified by transepithelial electrical resistance

2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 109-110
Author(s):  
Lauren L Kovanda ◽  
Monika Hejna ◽  
Yanhong Liu
Keyword(s):  
Butyric Acid ◽  
Sodium Butyrate ◽  
Barrier Function ◽  
Electrical Resistance ◽  
Intestinal Epithelial Cells ◽  
Intestinal Barrier ◽  
Transepithelial Electrical Resistance ◽  
Intestinal Barrier Function ◽  
Intestinal Epithelial

Abstract Intestinal barrier function in vitro is quantified by the transepithelial electrical resistance (TEER) across epithelial cell monolayers due to polarization and expression of tight junction proteins. The objective of the current study was to measure the TEER of porcine intestinal epithelial cells (IPEC-J2) treated with butyric acid, sodium butyrate, monobutyrin and tributyrin. MTT assays were performed for each compound to determine cell viability and appropriate treatment doses. Butyric acid and tributyrin treatments were: 0, 0.5, 1, 2, and 4 mM. Monobutyrin and sodium butyrate doses were: 0, 1, 2, 4, 8 mM. Cells were seeded at 5 × 105 cells/mL into 12-well plates on Corning transwell inserts. Cells were cultured for 4 to 5 days (until all wells had TEER close to 1000 Ωcm2) and were then treated with organic acids. Each compound was tested in a randomized complete block design with 10 replicates. TEER was measured in Ωcm2 using a Millicell ERS-2 voltohmmeter at 0 h (before treatment) and at 24, 48, and 72 h post-treatment. All data were analyzed by PROC MIXED of SAS. Butyric acid linearly enhanced (P < 0.001) TEER of IPEC-J2 dose-dependently, with the highest TEER observed at doses of 1 and 2 mM at each time point. Sodium butyrate did not impact TEER at h 24, but linearly increased (P < 0.05) TEER at h 48 and 72. Treatment of monobutyrin linearly improved (P < 0.001) TEER at h 24, 48, and 72, with the highest TEER observed at the dose of 8 mM. Tributyrin had the tendency to improve (P < 0.10) TEER at h 48 and 72 when the highest dose was applied. Results of the current in vitro study indicate that butyric acid and its derivatives may improve intestinal barrier function of pigs, which requires verification in vivo.

Desmoglein 2-mediated adhesion is required for intestinal epithelial barrier integrity

2010 ◽  
Vol 298 (5) ◽  
pp. G774-G783 ◽  
Author(s):  
Nicolas Schlegel ◽  
Michael Meir ◽  
Wolfgang-Moritz Heupel ◽  
Bastian Holthöfer ◽  
Rudolf E. Leube ◽  
...  
Keyword(s):  
Tight Junction ◽  
Intestinal Barrier ◽  
Intercellular Junctions ◽  
Barrier Properties ◽  
Epithelial Barrier ◽  
Intestinal Epithelial ◽  
Intestinal Epithelial Barrier ◽  
Barrier Functions ◽  
Epithelial Monolayers

The integrity of intercellular junctions that form the “terminal bar” in intestinal epithelium is crucial for sealing the intestinal barrier. Whereas specific roles of tight and adherens junctions are well known, the contribution of desmosomal adhesion for maintaining the intestinal epithelial barrier has not been specifically addressed. For the present study, we generated a desmoglein 2 antibody directed against the extracellular domain (Dsg2 ED) to test whether impaired Dsg2-mediated adhesion affects intestinal epithelial barrier functions in vitro. This antibody was able to specifically block Dsg2 interaction in cell-free atomic-force microscopy experiments. For in vitro studies of the intestinal barrier we used Caco2 cells following differentiation into tight enterocyte-like epithelial monolayers. Application of Dsg2 ED to Caco2 monolayers resulted in increased cell dissociation compared with controls in a dispase-based enterocyte dissociation assay. Under similar conditions, Dsg2 antibody significantly decreased transepithelial electrical resistance and increased FITC-dextran flux, indicating that Dsg2 interaction is critically involved in the maintenance of epithelial intestinal barrier functions. As revealed by immunostaining, this was due to Dsg2 ED antibody-induced rupture of tight junctions because tight junction proteins claudins 1, 4, and 5, occludin, and tight junction-associated protein zonula occludens-1 were partially removed from cell borders by Dsg2 ED treatment. Similar results were obtained by application of a commercial monoclonal antibody directed against the ED of Dsg2. Antibody-induced effects were blocked by absorption experiments using Dsg2-Fc-coated beads. Our data indicate that Dsg2-mediated adhesion affects tight junction integrity and is required to maintain intestinal epithelial barrier properties.

MicroRNA Determines the Fate of Intestinal Epithelial Cell Differentiation and Regulates Intestinal Diseases

2019 ◽  
Vol 20 (7) ◽  
pp. 666-673 ◽  
Author(s):  
Sujuan Ding ◽  
Gang Liu ◽  
Hongmei Jiang ◽  
Jun Fang
Keyword(s):  
Target Genes ◽  
Gastrointestinal Disease ◽  
Intestinal Barrier ◽  
Vital Role ◽  
Intestinal Barrier Function ◽  
Intestinal Epithelial ◽  
Intestinal Function ◽  
Cell Fates ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation

The rapid self-renewal of intestinal epithelial cells enhances intestinal function, promotes the nutritional needs of animals and strengthens intestinal barrier function to resist the invasion of foreign pathogens. MicroRNAs (miRNAs) are a class of short-chain, non-coding RNAs that regulate stem cell proliferation and differentiation by down-regulating hundreds of conserved target genes after transcription via seed pairing to the 3' untranslated regions. Numerous studies have shown that miRNAs can improve intestinal function by participating in the proliferation and differentiation of different cell populations in the intestine. In addition, miRNAs also contribute to disease regulation and therefore not only play a vital role in the gastrointestinal disease management but also act as blood or tissue biomarkers of disease. As changes to the levels of miRNAs can change cell fates, miRNA-mediated gene regulation can be used to update therapeutic strategies and approaches to disease treatment.

scholarly journals STAT3 Signalling via the IL-6ST/gp130 Cytokine Receptor Promotes Epithelial Integrity and Intestinal Barrier Function during DSS-Induced Colitis

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 187
Author(s):  
Lokman Pang ◽  
Jennifer Huynh ◽  
Mariah G. Alorro ◽  
Xia Li ◽  
Matthias Ernst ◽  
...  
Keyword(s):  
Barrier Function ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Intestinal Epithelial ◽  
Barrier Dysfunction ◽  
Epithelial Integrity ◽  
Barrier Integrity ◽  
Gp130 Receptor ◽  
Stat3 Signalling

The intestinal epithelium provides a barrier against commensal and pathogenic microorganisms. Barrier dysfunction promotes chronic inflammation, which can drive the pathogenesis of inflammatory bowel disease (IBD) and colorectal cancer (CRC). Although the Signal Transducer and Activator of Transcription-3 (STAT3) is overexpressed in both intestinal epithelial cells and immune cells in IBD patients, the role of the interleukin (IL)-6 family of cytokines through the shared IL-6ST/gp130 receptor and its associated STAT3 signalling in intestinal barrier integrity is unclear. We therefore investigated the role of STAT3 in retaining epithelial barrier integrity using dextran sulfate sodium (DSS)-induced colitis in two genetically modified mouse models, to either reduce STAT1/3 activation in response to IL-6 family cytokines with a truncated gp130∆STAT allele (GP130∆STAT/+), or by inducing short hairpin-mediated knockdown of Stat3 (shStat3). Here, we show that mice with reduced STAT3 activity are highly susceptible to DSS-induced colitis. Mechanistically, the IL-6/gp130/STAT3 signalling cascade orchestrates intestinal barrier function by modulating cytokine secretion and promoting epithelial integrity to maintain a defence against bacteria. Our study also identifies a crucial role of STAT3 in controlling intestinal permeability through tight junction proteins. Thus, therapeutically targeting the IL-6/gp130/STAT3 signalling axis to promote barrier function may serve as a treatment strategy for IBD patients.

scholarly journals Arctigenin fromFructus Arctii(Seed of Burdock) Reinforces Intestinal Barrier Function in Caco-2 Cell Monolayers

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Hee Soon Shin ◽  
Sun Young Jung ◽  
Su Yeon Back ◽  
Jeong-Ryong Do ◽  
Dong-Hwa Shon
Keyword(s):  
Barrier Function ◽  
Active Component ◽  
Inflammatory Diseases ◽  
Intestinal Barrier ◽  
Transepithelial Electrical Resistance ◽  
Intestinal Barrier Function ◽  
Intestinal Epithelial ◽  
Traditional Herbal Medicine ◽  
Cell Monolayers ◽  
Basolateral Side

Fructus Arctiiis used as a traditional herbal medicine to treat inflammatory diseases in oriental countries. This study aimed to investigate effect ofF. Arctiiextract on intestinal barrier function in human intestinal epithelial Caco-2 cells and to reveal the active component ofF. Arctii. We measured transepithelial electrical resistance (TEER) value (as an index of barrier function) and ovalbumin (OVA) permeation (as an index of permeability) to observe the changes of intestinal barrier function. The treatment ofF. Arctiiincreased TEER value and decreased OVA influx on Caco-2 cell monolayers. Furthermore, we found that arctigenin as an active component ofF. Arctiiincreased TEER value and reduced permeability of OVA from apical to the basolateral side but not arctiin. In the present study, we revealed thatF. Arctiicould enhance intestinal barrier function, and its active component was an arctigenin on the functionality. We expect that the arctigenin fromF. Arctiicould contribute to prevention of inflammatory, allergic, and infectious diseases by reinforcing intestinal barrier function.

Sign in / Sign up

Export Citation Format

Share Document