scholarly journals Xia-Yu-Xue Decoction Inhibits Intestinal Epithelial Cell Apoptosis in CCl4-Induced Liver Fibrosis

2017 ◽  
Vol 44 (1) ◽  
pp. 333-344 ◽  
Author(s):  
Wenting Ma ◽  
Le Tao ◽  
Wei Zhang ◽  
Yinshen Zhu ◽  
Dongying Xue ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Tight Junction ◽  
Intestinal Epithelial Cell ◽  
Intestinal Inflammation ◽  
Intestinal Epithelial ◽  
Tight Junction Proteins ◽  
Intestinal Epithelia ◽  
Epithelial Cell Apoptosis ◽  
Ccl4 Treatment ◽  
Junction Proteins

Background/Aims: Intestine-derived endotoxin is thought to play a role in the development of liver fibrosis. However, the pathological change in the intestine during liver fibrosis is still poorly understood. Here, we investigated the effects of Xia-yu-xue decoction (XYXD) on intestinal inflammation, apoptosis, and tight junction integrity in the carbon tetrachloride (CCl4)-induced liver fibrosis. Methods: Murine liver fibrosis was developed by CCI4 treatment three times per week over a 6-week period. The CCl4-treated mice were divided into two groups: the CCl4-water group (n=8, CCl4) and the CCl4-XYXD group (n=8, CCl4+XYXD). The CCl4+XYXD mice were treated with XYXD from the beginning of the first week. The expression of inflammatory cytokines and apoptotic molecules were examined using immunohistochemistry, real-time PCR, and western blot. The intestinal epithelial cell apoptosis was examined by TUNEL staining. The tight junction-related molecules, such as ZO-1, claudin, and occludin in the gut were measured by real-time PCR. Results: In CCl4-treated mice damage of the intestinal epithelia and infiltration of inflammatory cells into the lamina propria and muscular layer were observed. Proinflammatory markers MCP-1, TNF-α, CXCL11, IL-6, and CD68 were significantly increased in the intestinal epithelia in CCI4-treated mice. The expression of pro-apoptotic molecules including Fas and Bax was increased in the intestinal epithelia in CCI4-treated mice compared with that in control. The number of TUNEL-positive intestinal epithelial cells was also markedly increased in CCl4-treated mice. The expression of the tight junction proteins including ZO-1, claudin, and occludin was significantly decreased in CCI4-treated mice compared with that in control mice. Notably, XYXD treatment ameliorated increased inflammatory markers and apoptosis-related molecules and decreased tight-junction proteins in CCl4-treated mice. Conclusion: CCl4-treatment increased expression of proinflammatory cytokines and pro-apoptotic molecules and disrupted tight junction integrity in the intestine. XYXD treatment ameliorated intestinal inflammation, cell death, and tight junction disintegrity induced by CCl4 treatment, suggesting that XYXD inhibits CCl4-mediated liver fibrosis at least in part by ameliorating the intestinal epithelial damage.

Intestinal epithelial cell proliferation, apoptosis and expression of tight junction proteins in patients with obstructive jaundice

2010 ◽  
Vol 41 (2) ◽  
pp. 117-125 ◽  
Author(s):  
Stelios F. Assimakopoulos ◽  
Athanassios C. Tsamandas ◽  
Emanuel Louvros ◽  
Constantine E. Vagianos ◽  
Vassiliki N. Nikolopoulou ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Epithelial Cell ◽  
Obstructive Jaundice ◽  
Tight Junction ◽  
Intestinal Epithelial Cell ◽  
Intestinal Epithelial ◽  
Epithelial Cell Proliferation ◽  
Tight Junction Proteins ◽  
Junction Proteins

scholarly journals Tight Junction Proteins Claudin-2 and -12 Are Critical for Vitamin D-dependent Ca2+ Absorption between Enterocytes

2008 ◽  
Vol 19 (5) ◽  
pp. 1912-1921 ◽  
Author(s):  
Hiroki Fujita ◽  
Kotaro Sugimoto ◽  
Shuichiro Inatomi ◽  
Toshihiro Maeda ◽  
Makoto Osanai ◽  
...  
Keyword(s):  
Vitamin D ◽  
Tight Junction ◽  
Active Form ◽  
Intestinal Epithelial ◽  
Tight Junction Proteins ◽  
Dihydroxyvitamin D ◽  
Intestinal Epithelia ◽  
Junction Proteins

Ca2+ is absorbed across intestinal epithelial monolayers via transcellular and paracellular pathways, and an active form of vitamin D3, 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3], is known to promote intestinal Ca2+ absorption. However, the molecules driving the paracellular Ca2+ absorption and its vitamin D dependency remain obscure. Because the tight junction proteins claudins are suggested to form paracellular channels for selective ions between neighboring cells, we hypothesized that specific intestinal claudins might facilitate paracellular Ca2+ transport and that expression of these claudins could be induced by 1α,25(OH)2D3. Herein, we show, by using RNA interference and overexpression strategies, that claudin-2 and claudin-12 contribute to Ca2+ absorption in intestinal epithelial cells. We also provide evidence showing that expression of claudins-2 and -12 is up-regulated in enterocytes in vitro and in vivo by 1α,25(OH)2D3 through the vitamin D receptor. These findings strongly suggest that claudin-2- and/or claudin-12-based tight junctions form paracellular Ca2+ channels in intestinal epithelia, and they highlight a novel mechanism behind vitamin D-dependent calcium homeostasis.

Differential effects of EPA and DHA on DSS-induced colitis in mice and possible mechanisms involved

2021 ◽  
Author(s):  
Zhuangwei Zhang ◽  
Zhe Xue ◽  
Haitao Yang ◽  
Feng Zhao ◽  
Chundi Liu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Epithelial Cell ◽  
Tight Junction ◽  
Signaling Pathways ◽  
Intestinal Epithelial Cell ◽  
Intestinal Epithelial ◽  
Epithelial Cell Proliferation ◽  
Tight Junction Proteins ◽  
Inflammatory Signaling ◽  
Junction Proteins

EPA, superior to DHA, significantly attenuated DSS-induced colitis involved in promoting the expression of tight junction proteins, suppressing inflammatory signaling pathways and triggering intestinal epithelial cell proliferation.

Digestion of epithelial tight junction proteins by the commensal Clostridium perfringens

2013 ◽  
Vol 305 (10) ◽  
pp. G740-G748 ◽  
Author(s):  
Mihaela Pruteanu ◽  
Fergus Shanahan
Keyword(s):  
Epithelial Cell ◽  
Tight Junction ◽  
Clostridium Perfringens ◽  
Culture Supernatant ◽  
Dependent Manner ◽  
Intestinal Epithelial ◽  
Tight Junction Proteins ◽  
Epithelial Tight Junction ◽  
Junction Proteins ◽  
E Cadherin

The enteric microbiota contributes to the pathogenesis of inflammatory bowel disease, but the pathways involved and bacterial participants may vary in different hosts. We previously reported that some components of the human commensal microbiota, particularly Clostridium perfringens ( C. perfringens), have the proteolytic capacity for host matrix degradation and reduce transepithelial resistance. Here, we examined the C. perfringens-derived proteolytic activity against epithelial tight junction proteins using human intestinal epithelial cell lines. We showed that the protein levels of E-cadherin, occludin, and junctional adhesion molecule 1 decrease in colonic cells treated with C. perfringens culture supernatant. E-cadherin ectodomain shedding in C. perfringens-stimulated intestinal epithelial cells was detected with antibodies against the extracellular domain of E-cadherin, and we demonstrate that this process occurs in a time- and dose-dependent manner. In addition, we showed that the filtered sterile culture supernatant of C. perfringens has no cytotoxic activity on the human intestinal cells at the concentrations used in this study. The direct cleavage of E-cadherin by the proteases from the C. perfringens culture supernatant was confirmed by C. perfringens supernatant-induced in vitro degradation of the human recombinant E-cadherin. We conclude that C. perfringens culture supernatant mediates digestion of epithelial cell junctional proteins, which is likely to enable access to the extracellular matrix components by the paracellular pathway.

Differential gene expression of tight-junction proteins and their correlation with PRSS8 and prognosis in colorectal cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15548-e15548
Author(s):  
Wancai Yang ◽  
Yongchen Guo ◽  
Jim Lu ◽  
Yonghua Bao
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Tight Junction ◽  
Early Onset ◽  
Normal Mucosa ◽  
Colorectal Carcinogenesis ◽  
Tight Junction Proteins ◽  
Intestinal Epithelia ◽  
Differential Gene ◽  
Junction Proteins

e15548 Background: Intestinal epithelia cells are made up of tight junctions, adheren junctions and desmosomes. As integral membrane proteins, the tight junction proteins (TJPs) claudins (CLDNs) and occludin (OCLN) are the most important TJPs that play a major role in maintaining the integrity of the intestinal epithelia and regulate several key signaling pathways in cancers. Dysregulation of tight junction and adheren junction has been shown to be associated with disruption of mucosa barriers, chronic colitis, early onset of colorectal carcinogenesis, epithelial mesenchymal transition and cancer metastasis. Our recent studies have shown that intestinal conditional knockout of the Press8 (protease serine 8) gene causes disruption of intestinal epithelial homeostasis, spontaneous inflammation and tumorigenesis in mouse intestine. Whether these pathogeneses are resulted from TJPs alterations and their correlation with PRSS8 are largely unknown. Methods: PRSS8 overexpression plasmid was transfected into colon cancer cell line HCT116 cells and proteomics was conducted. The Cancer Genome Atlas colorectal cancer (CRC) data set was deeply mined, and the correlation between TJPs’ alterations, PRSS8 and prognosis was analyzed. Results: In vitro proteomics assay showed that increasing expression of PRSS8 led to differential expression of cellular TJPs and adheren proteins, including upregulation of E-cadherin, TJP1 (ZO-1) and OCLN, and downregulation of RAC1, CDC42, RHOA, CLDND1, ARHGAP1, CTNNB1 and CTNNBL1. TCGA data mining showed differential gene expression of tight junction proteins. For instance, similar as PRSS8, most colonic mucosal TJPs, such as TJP1 (ZO-1), TJP3, OLCN, CLDN7, CLDN8 and PTPRJ, were significantly decreased in CRC tissues (n = 215), compared to normal mucosa (n = 22). Moreover, these reduced expression of TJPs were positively correlated with the reduction of PRSS8 and were inversely associated with prognosis. In contrast, another group of TJPs, such as TJP2, CLDN1, CLDN2 and CLDN12, was significantly increased in CRC tissues in comparison with the normal mucosa. These increases of expression were negatively correlated with PRSS8 expression and poor outcomes. More interestingly, the PTPRJ, a newly identified tumor suppressor, was dramatically reduced in metastatic CRC, compared to the primary CRC. Furthermore, the reduced expression of PTPRJ was linked to poor prognosis in the CRC patients. The underlying mechanisms of regulatory interaction between PRSS8 and TJPs are under investigation. Conclusions: TJPs are differentially expressed in CRC and the alterations were well correlated with PRSS8 and prognosis. Therefore, these two opposite groups of TJPs could be used as biomarkers for the monitoring of early onset colorectal carcinogenesis, progression and for the prediction of prognosis.

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.

Red wine extract preserves tight junctions in intestinal epithelial cells under inflammatory conditions: implications for intestinal inflammation

2019 ◽  
Vol 10 (3) ◽  
pp. 1364-1374 ◽  
Author(s):  
Carla Nunes ◽  
Víctor Freitas ◽  
Leonor Almeida ◽  
João Laranjinha
Keyword(s):  
Red Wine ◽  
Intestinal Inflammation ◽  
Intestinal Barrier ◽  
Intestinal Epithelial ◽  
Tight Junction Proteins ◽  
Inflammatory Conditions ◽  
Inflammatory Stimuli ◽  
Wine Polyphenols ◽  
Red Wine Polyphenols ◽  
Junction Proteins

Red wine polyphenols protect the intestinal barrier against inflammatory stimuli by modulating the gene expression of key tight junction proteins.

scholarly journals Lactobacillus plantarum inhibits intestinal epithelial barrier dysfunction induced by unconjugated bilirubin

2010 ◽  
Vol 104 (3) ◽  
pp. 390-401 ◽  
Author(s):  
Yukun Zhou ◽  
Huanlong Qin ◽  
Ming Zhang ◽  
Tongyi Shen ◽  
Hongqi Chen ◽  
...  
Keyword(s):  
Tight Junction ◽  
Lactobacillus Plantarum ◽  
Laser Scanning Microscopy ◽  
Unconjugated Bilirubin ◽  
Epithelial Barrier ◽  
Intestinal Epithelial ◽  
Tight Junction Proteins ◽  
Intestinal Epithelial Barrier ◽  
Junction Protein ◽  
Junction Proteins

Although a large number of in vitro and in vivo tests have confirmed that taking probiotics can improve the intestinal barrier, few studies have focused on the relationship between probiotics and the intestinal epithelial barrier in hyperbilirubinaemia. To investigate the effects of and mechanisms associated with probiotic bacteria (Lactobacillus plantarum; LP) and unconjugated bilirubin (UCB) on the intestinal epithelial barrier, we measured the viability, apoptotic ratio and protein kinase C (PKC) activity of Caco-2 cells. We also determined the distribution and expression of tight junction proteins such as occludin, zonula occludens (ZO)-1, claudin-1, claudin-4, junctional adhesion molecule (JAM)-1 and F-actin using confocal laser scanning microscopy, immunohistochemistry, Western blotting and real-time quantitative PCR. The present study demonstrated that high concentrations of UCB caused obvious cytotoxicity and decreased the transepithelial electrical resistance (TER) of the Caco-2 cell monolayer. Low concentrations of UCB inhibited the expression of tight junction proteins and PKC but could induce UDP-glucuronosyltransferases 1 family-polypeptide A1 (UGT1A1) expression. UCB alone caused decreased PKC activity, serine phosphorylated occludin and ZO-1 levels. After treatment with LP, the effects of UCB on TER and apoptosis were mitigated; LP also prevented aberrant expression and rearrangement of tight junction proteins. Moreover, PKC activity and serine phosphorylated tight junction protein levels were partially restored after treatment with LP, LP exerted a protective effect against UCB damage to Caco-2 monolayer cells, and it restored the structure and distribution of tight junction proteins by activating the PKC pathway. In addition, UGT1A1 expression induced by UCB in Caco-2 cells could ameliorate the cytotoxicity of UCB.

Sign in / Sign up

Export Citation Format

Share Document