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 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.

Regulation of human epithelial tight junction proteins by Lactobacillus plantarum in vivo and protective effects on the epithelial barrier

2010 ◽  
Vol 298 (6) ◽  
pp. G851-G859 ◽  
Author(s):  
Jurgen Karczewski ◽  
Freddy J. Troost ◽  
Irene Konings ◽  
Jan Dekker ◽  
Michiel Kleerebezem ◽  
...  
Keyword(s):  
Tight Junction ◽  
Lactobacillus Plantarum ◽  
Transmembrane Protein ◽  
Intestinal Barrier ◽  
Protective Effects ◽  
Epithelial Tight Junction ◽  
Vitro Model ◽  
Probiotic Mechanisms

Lactobacillus plantarum , a commensal bacterium of humans, has been proposed to enhance the intestinal barrier, which is compromised in a number of intestinal disorders. To study the effect of L. plantarum strain WCFS1 on human barrier function, healthy subjects were administered L. plantarum or placebo in the duodenum for 6 h by means of a feeding catheter. The scaffold protein zonula occludens (ZO)-1 and transmembrane protein occludin were found to be significantly increased in the vicinity of the tight-junction (TJ) structures, which form the paracellular seal between cells of the epithelium. In an in vitro model of the human epithelium, L. plantarum induced translocation of ZO-1 to the TJ region; however, the effects on occludin were minor compared with those seen in vivo. L. plantarum was shown to activate Toll-like receptor 2 (TLR2) signaling, and treatment of Caco-2 monolayers with the TLR2 agonist Pam3-Cys-SK4(PCSK) significantly increased fluorescent staining of occludin in the TJ. Pretreatment of Caco-2 monolayers with L. plantarum or PCSK significantly attenuated the effects of phorbol ester-induced dislocation of ZO-1 and occludin and the associated increase in epithelial permeability. Our results identifying commensal bacterial stimulation of TLR2 in the gut epithelium as a regulator of epithelial integrity have important implications for understanding probiotic mechanisms and the control of intestinal homeostasis.

scholarly journals Layilin is critical for mediating hyaluronan 35 kDa-induced intestinal epithelial tight junction protein ZO-1 in vitro and in vivo

2018 ◽  
Vol 66 ◽  
pp. 93-109 ◽  
Author(s):  
Yeojung Kim ◽  
Gail A. West ◽  
Greeshma Ray ◽  
Sean P. Kessler ◽  
Aaron C. Petrey ◽  
...  
Keyword(s):  
Tight Junction ◽  
Tight Junction Protein ◽  
Intestinal Epithelial ◽  
Junction Protein ◽  
Epithelial Tight Junction

scholarly journals Intestinal epithelial barrier function and tight junction proteins with heat and exercise

2016 ◽  
Vol 120 (6) ◽  
pp. 692-701 ◽  
Author(s):  
Karol Dokladny ◽  
Micah N. Zuhl ◽  
Pope L. Moseley
Keyword(s):  
Heat Stress ◽  
Tight Junction ◽  
Barrier Function ◽  
Epithelial Barrier ◽  
Intestinal Epithelial ◽  
Tight Junction Proteins ◽  
Intestinal Epithelial Barrier ◽  
Epithelial Tight Junction ◽  
Junction Proteins

A single layer of enterocytes and tight junctions (intercellular multiprotein complexes) form the intestinal epithelial barrier that controls transport of molecules through transcellular and paracellular pathways. A dysfunctional or “leaky” intestinal tight junction barrier allows augmented permeation of luminal antigens, endotoxins, and bacteria into the blood stream. Various substances and conditions have been shown to affect the maintenance of the intestinal epithelial tight junction barrier. The primary focus of the present review is to analyze the effects of exertional or nonexertional (passive hyperthermia) heat stress on tight junction barrier function in in vitro and in vivo (animals and humans) models. Our secondary focus is to review changes in tight junction proteins in response to exercise or hyperthermic conditions. Finally, we discuss some pharmacological or nutritional interventions that may affect the cellular mechanisms involved in maintaining homeostasis of the intestinal epithelial tight junction barrier during heat stress or exercise.

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 The In Vitro Protective Role of Bovine Lactoferrin on Intestinal Epithelial Barrier

Molecules ◽  
2019 ◽  
Vol 24 (1) ◽  
pp. 148 ◽  
Author(s):  
Xiao Zhao ◽  
Xiao-Xi Xu ◽  
Yang Liu ◽  
En-Ze Xi ◽  
Jing-Jing An ◽  
...  
Keyword(s):  
Tight Junction ◽  
Barrier Function ◽  
Growth Promotion ◽  
Protective Role ◽  
Intestinal Barrier Function ◽  
Epithelial Barrier ◽  
Bovine Lactoferrin ◽  
Intestinal Epithelial ◽  
Intestinal Epithelial Barrier

The intestinal epithelial barrier plays a key protective role in the gut lumen. Bovine lactoferrin (bLF) has been reported to improve the intestinal epithelial barrier function, but its impact on tight junction (TJ) proteins has been rarely described. Human intestinal epithelial crypt cells (HIECs) were more similar to those in the human small intestine, compared with the well-established Caco-2 cells. Accordingly, both HIECs and Caco-2 cells were investigated in this study to determine the effects of bioactive protein bLF on their growth promotion and intestinal barrier function. The results showed that bLF promoted cell growth and arrested cell-cycle progression at the G2/M-phase. Moreover, bLF decreased paracellular permeability and increased alkaline phosphatase activity and transepithelial electrical resistance, strengthening barrier function. Immunofluorescence, western blot and quantitative real-time polymerase chain reaction revealed that bLF significantly increased the expression of three tight junction proteins—claudin-1, occludin, and ZO-1—at both the mRNA and protein levels, and consequently strengthened the barrier function of the two cell models. bLF in general showed higher activity in Caco-2 cells, however, HIECs also exhibited desired responses to barrier function. Therefore, bLF may be incorporated into functional foods for treatment of inflammatory bowel diseases which are caused by loss of barrier integrity.

scholarly journals Occludin regulates macromolecule flux across the intestinal epithelial tight junction barrier

2011 ◽  
Vol 300 (6) ◽  
pp. G1054-G1064 ◽  
Author(s):  
Rana Al-Sadi ◽  
Khaldun Khatib ◽  
Shuhong Guo ◽  
Dongmei Ye ◽  
Moustafa Youssef ◽  
...  
Keyword(s):  
Tight Junction ◽  
Intestinal Permeability ◽  
Transepithelial Resistance ◽  
Intestinal Epithelial ◽  
Knock Down ◽  
Large Channel ◽  
Epithelial Tight Junction ◽  
Mouse Intestine

Defective intestinal epithelial tight junction (TJ) barrier has been shown to be an important pathogenic factor contributing to the development of intestinal inflammation. The expression of occludin is markedly decreased in intestinal permeability disorders, including in Crohn's disease, ulcerative colitis, and celiac disease, suggesting that the decrease in occludin expression may play a role in the increase in intestinal permeability. The purpose of this study was to delineate the involvement of occludin in intestinal epithelial TJ barrier by selective knock down of occludin in in vitro (filter-grown Caco-2 monolayers) and in vivo (recycling perfusion of mouse intestine) intestinal epithelial models. Our results indicated that occludin small-interfering RNA (siRNA) transfection causes an increase in transepithelial flux of various-sized probes, including urea, mannitol, inulin, and dextran, across the Caco-2 monolayers, without affecting the transepithelial resistance. The increase in relative flux rate was progressively greater for larger-sized probes, indicating that occludin depletion has the greatest effect on the flux of large macromolecules. siRNA-induced knock down of occludin in mouse intestine in vivo also caused an increase in intestinal permeability to dextran but did not affect intestinal tissue transepithelial resistance. In conclusion, these results show for the first time that occludin depletion in intestinal epithelial cells in vitro and in vivo leads to a selective or preferential increase in macromolecule flux, suggesting that occludin plays a crucial role in the maintenance of TJ barrier through the large-channel TJ pathway, the pathway responsible for the macromolecule flux.

scholarly journals Impaired Gut Epithelial Tight Junction Expression in Hemodialysis Patients Complicated with Intradialytic Hypotension

2018 ◽  
Vol 2018 ◽  
pp. 1-6
Author(s):  
Tsai-Kun Wu ◽  
Paik-Seong Lim ◽  
Jong-Shiaw Jin ◽  
Ming-Ying Wu ◽  
Chang-Hsu Chen
Keyword(s):  
Tight Junction ◽  
Intestinal Barrier ◽  
Intradialytic Hypotension ◽  
Intestinal Epithelial ◽  
Advanced Chronic Kidney Disease ◽  
Epithelial Tight Junction ◽  
Group 3 ◽  
Group 2 ◽  
The Impact ◽  
Group 1

Background. There is accumulating evidence pointing to uremia-induced impairment of the intestinal epithelial barrier structure in advanced chronic kidney disease (CKD) and hemodialysis (HD) patients. In this study, the impact of intradialytic hypotension on intestinal barrier integrity is being explored. Methods. Immunohistochemical staining was used to detect the expression of 4 types of tight junction (TJ) proteins such as occludin, zonula occludens-1 (ZO-1), claudin-1, and claudin-4, in colonic samples of a group of patients receiving segmental colectomy. Five patients with nondialysis CKD (group 2), 5 HD patients with intradialytic hypotension (group 3), and 5 non-CKD subjects (group 1) were examined. Results. Both patients’ groups 2 and 3 demonstrated significantly reduced expression of occludin as compared to group 1 (p<0.05 and p<0.01, resp.). Except for claudin-4, expression of all markers of TJ proteins was significantly reduced in patients’ group 3 as compared to control (p<0.01). In addition, decreased expressions of claudin-1 and ZO-1 were also more pronounced in group 3 when compared to group 2. Conclusions. This study extends the earlier finding by demonstrating that dialysis-related hypotension caused even marked depletion of the key protein constituents of the epithelial TJ.

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