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Lateolabrax maculatus iridovirus (LMIV) is a variant strain of red sea bream iridovirus (RSIV), causing serious economic losses in aquaculture. Claudins (CLDNs) are major components of tight junctions (TJs) forming an important line of defense against pathogens. Our pilot miRNA-mRNA joint analysis indicated the degradation of CLDN3, as well as its interaction with miR-181a during LMIV infection. To elucidate the miR-181a/CLDN3/LMIV interactions, in vitro assays were carried out on LMB-L cells. We first confirmed that LMIV infection could decrease the expression of CLDN3, accompanied by the enhancement of permeability, suggesting the dysfunction of TJs. Contrary to the inhibition of CLDN3, the activation of miR-181a was proved, presenting a negative correlation between miR-181a and CLDN3 (Pearson r = −0.773 and p < 0.01). In addition, the influence of CLDN3 on LMIV replication was analyzed by knockdown and over-expression of CLDN3. When CLDN3 was silenced in LMB-L cells with siCLDN3-623 at 9 days post transfection (dpt), LMIV copies and titers were significantly up-regulated by 1.59-fold and 13.87-fold, respectively. By contrast, LMIV replication in LMB-L cells was reduced by 60% and 71%, post transfection with pcDNA3.1-CLDN3 over-expressed plasmid at 6 dpt and 9 dpt, respectively. Ultimately, the regulatory relationship between miR-181a and CLDN3 was further validated by dual luciferase reporter assays. Taking into account the above-described results, we proposed a "miR-181a/CLDN3/LMIV" regulatory relationship. This study provides a new insight for understanding the mechanism of LMIV replication. [ABSTRACT FROM AUTHOR]

Glycosylated mucin proteins contribute to the essential barrier function of the intestinal epithelium. The transmembrane mucin MUC13 is an abundant intestinal glycoprotein with important functions for mucosal maintenance that are not yet completely understood. We demonstrate that in human intestinal epithelialmonolayers, MUC13 localized to both the apical surface and the tight junction (TJ) region on the lateral membrane. MUC13 deletion resulted in increased transepithelial resistance (TEER) and reduced translocation of small solutes. TEER buildup in ΔMUC13 cells could be prevented by addition of MLCK, ROCK or protein kinase C (PKC) inhibitors. The levels of TJ proteins including claudins and occludin were highly increased in membrane fractions of MUC13 knockout cells. Removal of the MUC13 cytoplasmic tail (CT) also altered TJ composition but did not affect TEER. The increased buildup of TJ complexes in ΔMUC13 and MUC13-ΔCT cells was dependent on PKC. The responsible PKC member might be PKCd (or PRKCD) based on elevated protein levels in the absence of full-length MUC13. Our results demonstrate for the first time that a mucin protein can negatively regulate TJ function and stimulate intestinal barrier permeability. [ABSTRACT FROM AUTHOR]

Lateolabrax maculatus iridovirus (LMIV) is a variant strain of red sea bream iridovirus (RSIV), causing serious economic losses in aquaculture. Claudins (CLDNs) are major components of tight junctions (TJs) forming an important line of defense against pathogens. Our pilot miRNA-mRNA joint analysis indicated the degradation of CLDN3, as well as its interaction with miR-181a during LMIV infection. To elucidate the miR-181a/CLDN3/LMIV interactions, in vitro assays were carried out on LMB-L cells. We first confirmed that LMIV infection could decrease the expression of CLDN3, accompanied by the enhancement of permeability, suggesting the dysfunction of TJs. Contrary to the inhibition of CLDN3, the activation of miR-181a was proved, presenting a negative correlation between miR-181a and CLDN3 (Pearson r = −0.773 and p < 0.01). In addition, the influence of CLDN3 on LMIV replication was analyzed by knockdown and over-expression of CLDN3. When CLDN3 was silenced in LMB-L cells with siCLDN3-623 at 9 days post transfection (dpt), LMIV copies and titers were significantly up-regulated by 1.59-fold and 13.87-fold, respectively. By contrast, LMIV replication in LMB-L cells was reduced by 60% and 71%, post transfection with pcDNA3.1-CLDN3 over-expressed plasmid at 6 dpt and 9 dpt, respectively. Ultimately, the regulatory relationship between miR-181a and CLDN3 was further validated by dual luciferase reporter assays. Taking into account the above-described results, we proposed a “miR-181a/CLDN3/LMIV” regulatory relationship. This study provides a new insight for understanding the mechanism of LMIV replication.

Objective To investigate the expression and clinical significance of serum Claudin-1 and Claudin-3 levels in patients with psoriasis vulgaris (PV). Methods A total of 122 patients with PV were enrolled as the PV group (including 36 cases in the mild group, 54 cases in the moderate group, 32 cases in the severe group), and 60 healthy controls were enrolled from the physical examination center. The serum levels of hypersensitive C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), interleukin6 (IL-6), Claudin-1 and Claudin-3 were measured using enzyme linked immunosorbent assay (ELISA). Logistic regression was used to analyze the relationship between serum levels of Claudin-1 and Claudin-3 and PV severity, and the receiver operating characteristic (ROC) curve was used to analyze its diagnostic value. Results The levels of hs-CRP, TNF-α and IL-6 in PV group were significantly higher than that in the controls (P

Glioblastoma multiforme (GBM) is a significantly malignant and lethal brain tumor with an average survival time of less than 12 months. Several researches had shown that Claudin-3 (CLDN3) is overexpressed in various cancers and might be important in their growth and spread. In this study, we used qRT-PCR, western blotting, immunohistochemistry, and immunofluorescence staining assays to investigate the expression levels of various proteins. To explore the proliferation abilities of GBM cells, we conducted the CCK-8 and EdU-DNA formation assays. Wound healing and transwell assays were used to investigate the capacities of invasion and migration of GBM cells. Additionally, we constructed an intracranial xenograft model of GBM to study the in vivo role of CLDN3. Our study devoted to investigate the function of CLDN3 in the pathogenesis and progression of GBM. Our study revealed that CLDN3 was upregulated in GBM and could stimulate tumor cell growth and epithelial-mesenchymal transition (EMT) in both laboratory and animal models. We also discovered that CLDN3 expression could be triggered by transforming growth factor-β (TGF-β) and reduced by specific inhibitors of the TGF-β signaling pathway, such as ITD-1. Further analysis revealed that increased CLDN3 levels enhanced TGF-β-induced growth and EMT in GBM cells, while reducing CLDN3 levels weakened these effects. Our study demonstrated the function of CLDN3 in facilitating GBM growth and metastasis and indicated its involvement in the tumorigenic effects of TGF-β. Developing specific inhibitors of CLDN3 might, therefore, represent a promising new approach for treating this devastating disease. [ABSTRACT FROM AUTHOR]

Objective To investigate the expression and clinical significance of serum Claudin-1 and Claudin-3 levels in patients with psoriasis vulgaris (PV). Methods A total of 122 patients with PV were enrolled as the PV group (including 36 cases in the mild group, 54 cases in the moderate group, 32 cases in the severe group), and 60 healthy controls were enrolled from the physical examination center. The serum levels of hypersensitive C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), interleukin6 (IL-6), Claudin-1 and Claudin-3 were measured using enzyme linked immunosorbent assay (ELISA). Logistic regression was used to analyze the relationship between serum levels of Claudin-1 and Claudin-3 and PV severity, and the receiver operating characteristic (ROC) curve was used to analyze its diagnostic value. Results The levels of hs-CRP, TNF-α and IL-6 in PV group were significantly higher than that in the controls (P<0.05). The serum levels of Claudin-1 in the PV group were significantly lower than that in the controls (t=11.96, P<0.001), while the serum levels of Claudin-3 was significantly higher in the PV group (t=10.64, P<0.001). The serum levels of Claudin-1 were negatively correlated with disease severity(r=-0.38), hs-CRP(r=-0.18) and TNF-α levelsm(r=-0.22) (all P<0.05). In contrast, serum levels of Claudin-3 were positively correlated with disease severity(r=0.41), and serum levels of hs-CRP(r=0.20), TNF-α(r=0.18) and IL-6 (r=0.36) (all P<0.05). Moreover, serum levels of Claudin-1 were negatively correlated with Claudin-3 (r=-0.22, P=0.015). The areas under the curve of Claudin-1 and Claudin-3 for the diagnosis of PV were 0.875 and 0.867, respectively, which were significantly higher than that of TNF-α (Z values were 4.16 and 3.60, respectively, P<0.001) and IL-6 (Z values were 3.63, 3.52, respectively, P<0.001). Conclusions The altered expression levels of serum Claudin-1 and Claudin-3 in PV patients are associated with disease severity and the levels of inflammatory markers. Alterations of Claudin-1 and Claudin-3 expression are independent risk factors for PV. Serum levels of Claudin-1 and Claudin-3 have some diagnostic value for PV. [ABSTRACT FROM AUTHOR]

Ovarian cancer (OC) is a gynecological malignancy that ranks among the most common female cancers worldwide and notably reduces a patient's quality of life. Mitochondrial carrier homology 2 (MTCH2) is a mitochondrial outer membrane protein that serves a regulatory role in mitochondrial metabolism and cell death. The precise contribution and underlying molecular pathways of MTCH2 in the context of OC development is currently unclear. The present study aimed to investigate the roles of MTCH2 in the energy metabolism, cell proliferation and metastatic potential of OC cells and evaluate the regulatory relationship between MTCH2, aminoacyl transfer RNA synthetase-interacting multifunctional protein 2 (AIMP2) and claudin-3. An analysis of 67 patients with high-grade serous OC demonstrated increased expression levels of MTCH2, AIMP2 and claudin-3 in OC tumor tissue samples compared with in corresponding normal tissues adjacent to OC tissue samples. MTCH2 overexpression was significantly associated with the International Federation of Gynecology and Obstetrics stage and tumor differentiation of the OC tumor samples. In vitro experiments using the SK-OV-3 OC cell line demonstrated that MTCH2 exerts a regulatory effect on the cell proliferation, invasion and migratory capabilities of these cells. Knockdown of MTCH2 reduced ATP production, induced mitochondrial dysfunction and promoted cytoskeleton remodeling and apoptosis in SK-OV-3 OC cells. In addition, MTCH2 knockdown downregulated the expression levels of both claudin-3 and AIMP2 proteins. Knockdown of AIMP2 inhibited the regulatory effect of MTCH2. Co-immunoprecipitation experiments demonstrated that MTCH2 interacts with AIMP2 and claudin-3. The present study provides novel insights into the treatment of OC metastasis, as MTCH2 was demonstrated to serve roles in the progression of OC cells through the regulation of claudin-3 via AIMP2, which could provide novel insights into the treatment of ovarian cancer metastasis. [ABSTRACT FROM AUTHOR]

The integrity of the lymphatic system is critical for preventing the dissemination of tumor cells, such as melanoma, to distant parts of the body. IFN-γ is well studied as a negative regulator for lymphangiogenesis, which is strongly associated with cancer metastasis. However, the exact mechanisms underlying this process remain unclear. In the present study, we investigated whether IFN-γ signaling in lymphatic endothelial cells (LECs) affects tumor cell dissemination by regulating the barrier function of tumor-associated lymphatic vessels. Using LEC-specific IFN-γ receptor (IFN-γR) knockout mice, we found that the loss of IFN-γR in LECs increased the dissemination of melanoma cells into the draining lymph nodes. Notably, IFN-γ signaling in LECs inhibited trans-lymphatic endothelial cell migration of melanoma cells, indicating its regulation of lymphatic barrier function. Further investigations revealed that IFN-γ upregulated the expression of the tight junction protein Claudin-3 in LECs, while knockdown of Claudin-3 in LECs abolished IFN-γ-induced inhibition of trans-lymphatic endothelial migration activity. Mechanistically, IFN-γ inhibits AMPK signaling activation, which is involved in the regulation of fatty acid metabolism. Modulating fatty acid metabolism and AMPK activation in LECs also affected the lymphatic dissemination of melanoma cells, further confirming that this process is involved in IFN-γ-induced regulation of lymphatic barrier function. These results provide novel insights into how IFN-γ modulates tight junctions in LECs, inhibiting the dissemination of melanoma cells via the lymphatic vessels. [Display omitted] • Lymphatic-specific loss of IFN-γ receptor promoted lymph node metastasis of melanoma cells. • IFN-γ signaling in LECs promoted lymphatic barrier function to inhibit melanoma lymphatic dissemination. • IFN-γ regulates the expression of tight junction protein Claudin-3 in LECs to affect vessel integrity. • AMPK signaling and fatty acid metabolism in LECs mediated by IFN-γ contribute to maintaining lymphatic barrier function. [ABSTRACT FROM AUTHOR]

Background and purposeNecrotizing enterocolitis (NEC) is a critical gastrointestinal disease. We aim to explore the value of fecal human β-defensin 2 (HBD-2), Claudin-3, high-mobility group box-1 protein (HMGB-1), and resistin-like molecule β (Relmβ) as well as some laboratory metrics to predict the deterioration of NEC.MethodsInfants diagnosed with NEC at Stage II were enrolled in our study. Those who progressed to Stage III were included in the Stage III group and the rest were included in the Stage II group. Clinical data and laboratory metrics of the infants were collected. Fecal samples of HBD2, HMGB-1, Claudin-3, and Relmβ collected during their enrollment were determined by using enzyme-linked immunosorbent assay (ELISA) kits. Student's t-test, the Mann–Whitney U test, the chi-square test, receiver operating characteristic (ROC), and logistic regression analysis were performed.ResultsSixty infants diagnosed with NEC at Stage II were enrolled in our study, with 27 in the Stage III group (n = 27) and 33 in the Stage II group (n = 33). Although many of these NEC cases were late preterm and term infants, the infants in the Stage III group had a lower gestational age (P

Claudin-3 (CLDN3), a tight junction protein, regulates cell-to-cell interactions in epithelial or endothelial cell sheets. During tumorigenesis, epithelial cells are transformed, and tumor cells proliferate through out-of-plane division, resulting in external exposure of CLDN3. Since alterations of CLDN3 expression are associated with cancer progression and higher CLDN3 expression is observed in most ovarian cancers, we tested the feasibility of using a CLDN3-specific antibody as a novel imaging tracer. After reducing the CLDN3-specific antibodies to expose the –SH groups, click chemistry was used to conjugate the radioactive isotope 111In or the fluorescent protein FNR648. Human ovarian cancer OVCAR-3 and glioblastoma U87MG cells were used as CLDN3-positive and -negative cells. Flow cytometry was used to determine the CLDN3 IgG1 monoclonal antibody binding to both cell lines. OVCAR-3 cells were injected subcutaneously into mice to establish a xenograft model. 111In-labeled CLDN3 antibodies (370 kBq/50 μL) were administered intravenously into mice. After 24 h, organs, including tumors, were excised and measured with a γ-counter. Images were acquired with the IVIS optical imaging system and SPECT/CT. The labeling efficiency of NOTA-111In and antibody-NOTA-111In was 98.52% and 100%, respectively. FNR648-labeled CLDN3 antibody bound to the cell surface of OVCAR-3 and U87MG with 83.4% and 5.7% specificity, respectively. In OVCAR-3 tumor xenografted mice, CLDN3 IgG1 antibody showed a 2.5-fold higher tumor uptake (20.4 ± 7.4% ID/g) than human IgG1 (8.8 ± 2.6% ID/g) at 24 h post injection. The CLDN3 antibody fluorescence signal in the tumor peaked at 24 h post injection. We have successfully conjugated a radioisotope and a fluorescent protein with CLDN3-specific antibodies and verified the specific binding of labeled antibodies to OVCAR-3 tumors in a mouse model. Our data suggested that CLDN3-specific human monoclonal antibodies could be used as a useful theranostic tracer [Display omitted] [ABSTRACT FROM AUTHOR]

Claudin-3是 Claudin紧密连接蛋白家族的成员之一, 也是组成细胞间紧密连接的重要蛋白分 子, 在组成紧密连接的血脑物理屏障和维持细胞环境稳定性方面具有重要作用。其表达的失衡会导致紧密连 接遭到破坏, 血脑物理屏障功能和分子之间的传递功能受到损伤, 导致多种组织和细胞发生相应疾病, 尤其和 神经系统、胆固醇结石和肿瘤等疾病的关系显著。作者就目前有关 Claudin-3的研究进展进行了综述, 以便临 床了解 Claudin-3在相关疾病检测、诊断、治疗及预后判断方面的重要性. [ABSTRACT FROM AUTHOR]

We implemented a multi-pronged strategy (MAX) involving chronic (2 weeks high carbohydrate [CHO] diet + gut-training) and acute (CHO loading + 90 g·h−1 CHO during exercise) strategies to promote endogenous and exogenous CHO availability, compared with strategies reflecting lower ranges of current guidelines (CON) in two groups of athletes. Nineteen elite male race walkers (MAX: 9; CON:10) undertook a 26 km race-walking session before and after the respective interventions to investigate gastrointestinal function (absorption capacity), integrity (epithelial injury), and symptoms (GIS). We observed considerable individual variability in responses, resulting in a statistically significant (p < 0.001) yet likely clinically insignificant increase (Δ 736 pg·mL−1) in I-FABP after exercise across all trials, with no significant differences in breath H2 across exercise (p = 0.970). MAX was associated with increased GIS in the second half of the exercise, especially in upper GIS (p < 0.01). Eighteen highly trained male and female distance runners (MAX: 10; CON: 8) then completed a 35 km run (28 km steady-state + 7 km time-trial) supported by either a slightly modified MAX or CON strategy. Inter-individual variability was observed, without major differences in epithelial cell intestinal fatty acid binding protein (I-FABP) or GIS, due to exercise, trial, or group, despite the 3-fold increase in exercise CHO intake in MAX post-intervention. The tight-junction (claudin-3) response decreased in both groups from pre- to post-intervention. Groups achieved a similar performance improvement from pre- to post-intervention (CON = 39 s [95 CI 15–63 s]; MAX = 36 s [13–59 s]; p = 0.002). Although this suggests that further increases in CHO availability above current guidelines do not confer additional advantages, limitations in our study execution (e.g., confounding loss of BM in several individuals despite a live-in training camp environment and significant increases in aerobic capacity due to intensified training) may have masked small differences. Therefore, athletes should meet the minimum CHO guidelines for training and competition goals, noting that, with practice, increased CHO intake can be tolerated, and may contribute to performance outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Although collecting faeces and blood samples are considered non-invasive methods of monitoring Crohn’s disease (CD), these methods are less preferred by some patients. This study utilized urine as an alternative to evaluate four disease biomarkers in young adults with active CD before and after exclusive enteral nutrition (EEN) therapy. Methods: Urine samples collected at baseline (W0) and after 8 weeks (W8) of EEN therapy were assayed by ELISA for levels of intestinal fatty acid-binding protein (I-FABP), liver fatty acid-binding protein (L-FABP), claudin-3, and calprotectin. Levels of each biomarker were also compared with standard clinical parameters, including disease indexes, nutrient, and inflammatory markers. Results: Of the paired urine samples from 14 patients, 10 were female and 12 were newly diagnosed with CD. Urinary I-FABP:Cr (standardized to urine Cr) levels were significantly reduced, while urinary L-FABP:Cr levels increased following EEN therapy. Urinary L-FABP:Cr correlated positively with serum insulin-like growth factor 1 (IGF-1) (r = 0.60, p = 0.02). Urinary CLND3:Cr and calprotectin:Cr levels were not significantly different after treatment. Conclusion: I-FABP is a potential urinary biomarker of disease activity in adults with CD, while urinary L-FABP may be an indirect marker of nutritional status in adults with CD. CLND3 and calprotectin do not appear to have roles as urinary biomarkers in CD. These findings warrant further investigations using a larger sample size.

The membrane protein claudin-3 (CLDN3) is critical for the formation and maintenance of tight junction and its high expression has been implicated in dictating malignant progression in various cancers. However, the post-translational modification of CLDN3 and its biological function remains poorly understood. Here, we report that CLDN3 is positively correlated with ovarian cancer progression both in vitro and in vivo. Of interest, CLDN3 undergoes S-palmitoylation on three juxtamembrane cysteine residues, which contribute to the accurate plasma membrane localization and protein stability of CLDN3. Moreover, the deprivation of S-palmitoylation in CLDN3 significantly abolishes its tumorigenic promotion effect in ovarian cancer cells. By utilizing the co-immunoprecipitation assay, we further identify ZDHHC12 as a CLDN3-targating palmitoyltransferase from 23 ZDHHC family proteins. Furthermore, the knockdown of ZDHHC12 also significantly inhibits CLDN3 accurate membrane localization, protein stability and ovarian cancer cells tumorigenesis. Thus, our work reveals S-palmitoylation as a novel regulatory mechanism that modulates CLDN3 function, which implies that targeting ZDHHC12-mediated CLDN3 S-palmitoylation might be a potential strategy for ovarian cancer therapy.

Background: Metastasis is the worst prognostic variable of patients with colorectal cancer (CRC). For the development of metastases, it is necessary that cancer cells detach from the primary tumor, migrate into the angiolymphatic system, and invade the tissue where they will develop. The breakdown of the tight junctions (TJs) plays an important role in colorectal metastatic tumors. Claudin-3 and occludin are the main component proteins of TJs. Aim: To analyze the expression and tissue content of claudin-3 and occludin in normal and neoplastic tissues of patients with metastatic CRC. Methods: Fifty-seven consecutive patients with stage III and IV CRC were included. Fragments of neoplastic tissue were collected from the tumor margins, and samples of the normal tissue were collected from the same patient in a standardized distance of 10 cm from the cranial margin of the tumor. Immunohistochemistry technique was used to identify the tissue staining of claudin-3 and occludin. To measure the content of both proteins in cellular membranes of normal and cancer cells, a validated immunoscore was used. Results: Claudin-3 and occludin in normal tissues are in the apical and lateral membranes of cells, while in the neoplastic, in cytoplasm. The mean of the tissue content of claudin-3 in the normal tissue was 2.57 ± 0.16, while in the neoplastic tissue was 1.03 ± 0.13. The contents of occludin were 2.77 ± 0.1 in normal tissue, while in the neoplastic were 1.08 ± 0.14. Conclusion: There is a reduction in the content of the claudin-3 and occludin in the cell membranes of the neoplastic tissue in patients with CRC. [ABSTRACT FROM AUTHOR]

Historically, children evaluated for vomiting and diarrhea secondary to viral enteritis have symptoms lasting 2–4 days and respond to supportive care, including oral rehydration and anti-emetics if required. Recently, within a 14-day timespan, we encountered three children with severe diarrhea who rapidly became dehydrated and went into hypotensive shock. Although SARS-CoV-2 molecular tests were negative by nasopharyngeal swab, all were later found to have MIS-C. This small case series underscores features reported in previous larger studies and emphasizes the rapid clinical evolution of this condition. We highlight the importance of early recognition of cardinal laboratory findings characteristic of MIS-C (i.e., lymphopenia, markedly elevated acute phase reactants, and hypoalbuminemia). We also show serologic evidence that the pathophysiological mechanism of SARS-CoV-2 related diarrhea may differ from other causes of dehydrating vomiting and diarrhea, with no serologic evidence of villus cell injury.

Background and Aim: Portal hypertensive gastropathy (PHG) is characterized by noninflammatory edema and vasodilatation of the lamina propria of the mucosal epithelium. In addition, the alterations of intercellular junction proteins and dilatation of the endothelial gaps have been reported. In this study, we examined whether irsogladine maleate (IM), a gastric mucosal protective agent, has the potential to improve PHG by restoration of tight junctions (TJs). Methods: Twenty‐four patients with PHG were registered and randomly assigned into two groups: 12 patients in the IM‐administration group and 12 patients in the non‐administration group. In the administration group, IM (4 mg/day) was administered orally for 12 weeks. Gastric mucosa with a red color in patients with PHG were obtained endoscopically on the registration day and 12 weeks later. The endoscopic findings were evaluated, an immunohistochemical analysis of claudin‐3 (a TJ protein) expression in gastric mucosal tissues by a laser microscope was performed, and claudin‐3 expression was quantified by western blot analysis. Results: Irsogladine maleate improved the degree of PHG in 2/12 patients endoscopically, in contrast to none of the 12 patients in the non‐administration group. Immunohistochemical analysis showed that expression of claudin‐3 increased in 8/12 patients in the IM‐administration group and 2/12 patients in the non‐administration group (P = 0.036). Western blot analysis revealed that the increase in claudin‐3 after 12 weeks was significantly higher in the IM‐administration group than in the non‐administration group (P = 0.010). Conclusions: The present pilot study suggested that IM might improve the gastric mucosa in PHG through restoration of TJ‐protein claudin‐3. [ABSTRACT FROM AUTHOR]

Background: Psoriasis is a common inflammatory disorder of the skin. Psoriasis is a disease of multifactorial origin where certain environmental factors acting on individuals with specific genetic predisposition leads to an immune dysregulation. Claudins are transmembrane proteins, which participate in the formation of tight junctions by binding to the actin cytoskeleton. Claudin-3 present in the blood is considered as a useful biomarker of intestinal permeability. Objective: To evaluate serum level of claudin-3 in patients with psoriasis in comparison to control group and correlate its levels with disease severity. Patients and methods: Fifty-three patients (32 males and 21 females) with psoriasis and forty normal healthy control (23 males and 17 females) who matched the cases group as regard age and sex were included in this work. They were randomly selected from the Dermatology Department outpatient clinic in Mansoura University Hospital. Results: Psoriasis group showed significantly higher level of claudin-3 when compared to control group (mean=58.3 versus 41.2; p<0.001). Smoking was significantly associated with higher Claudin-3 level (p=0.031). In addition, claudin-3 level increased gradually with increased severity grades (p<0.001). No significant associations were found regarding claudin-3 level according to gender, nutritional status, family history, in psoriasis group (p>0.05 for each). Higher BMI, smoking and higher claudin-3 level were associated with prediction of higher PASI score in univariate analysis. While multivariate analysis revealed that only smoking and higher claudin-3 level were considered independent predictor of more severe psoriasis cases. Conclusion: Claudin-3 level was significantly higher in patients with psoriasis than healthy controls. PASI correlated with claudin-3 levels. [ABSTRACT FROM AUTHOR]

Claudins are essential components of tight junctions, which are frequently deregulated in breast cancer. The aim of the current study was to assess claudin-3 and -4 expression in bilateral breast cancer (BBC) and unilateral breast cancer (UBC). Immunohistochemical expression of claudin-3 and claudin-4 was evaluated in tissue microarrays containing 174 cases of BBCs paired with 174 cases of solitary tumors. Each case was classified as claudin-high or claudin-low depending on the H-score value. The results were correlated with histopathological features and the expression of basic breast cancer biomarkers. Median H-scores for claudin-3 were significantly higher in the synchronous BBC (sBBC) than in UBC. Claudin-4-high cases were more prevalent than within the whole BBC group, and sBBC and metachronous BBC (mBBC) alone. In the BBC group negative ER, high Ki-67 and high claudin-3 were independent factors correlated with high claudin-4. In the UBC group, Ki-67 >14% and high claudin-3 were associated with high claudin-4. Our study demonstrates that the expression of claudin-4 is significantly higher in UBC compared to BBC tumors. We also demonstrated that high claudin-4 expression in BBC is associated with a more aggressive phenotype (lack of steroid receptors, HER2 overexpression, and high Ki-67). It is possible that claudins down- and upregulation may depend on different triggers and lead to various consequences in UBC and BBC. [ABSTRACT FROM AUTHOR]

In lactating mammary glands, tight junctions (TJs) prevent blood from mixing with milk and maintain epithelial cell polarity, which is important for milk production. This study aimed to investigate the effect of sodium acetate and sodium butyrate (SB) stimulation direction on the TJ barrier function, which is measured with regard to transepithelial electrical resistance and fluorescein flux, in goat mammary epithelial cells. The expression and localization of the TJ proteins claudin-3 and claudin-4 were examined using Western blotting and immunofluorescence. SB treatment in the lower chamber of cell culture inserts adversely affected the TJ barrier function, whereas sodium acetate barely had any effect, regardless of stimulation direction. In addition, SB treatment in the lower chamber significantly upregulated claudin-3 and claudin-4, whereas TJ proteins showed intermittent localization. Moreover, SB induced endoplasmic reticulum (ER) stress. ARC155858, a monocarboxylate transporter-1 inhibitor, alleviated the adverse impact of SB on TJs and the associated ER stress. Interestingly, sodium β-hydroxybutyrate, a butyrate metabolite, did not affect the TJ barrier function. Our findings indicate that sodium acetate and SB influence the TJ barrier function differently, and excessive cellular uptake of SB can disrupt TJs and induce ER stress., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The extent of tight junction (TJ) formation is one of many factors that regulate motility, invasion, and metastasis. Claudins are required for the formation and maintenance of TJs. Claudin-3 (CLDN3) and claudin-4 (CLDN4) are highly expressed in the majority of ovarian cancers. We report here that CLDN3 and CLDN4 each serve to constrain the growth of human 2008 cancer xenografts and limit metastatic potential. Knockdown of CLDN3 increased in vivo growth rate by 2.3-fold and knockdown of CLDN4 by 3.7-fold in the absence of significant change in in vitro growth rate. Both types of tumors exhibited increase in birth rate as measured by Ki67 staining and decrease in death rate as reflected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. Knockdown of either claudin did not alter expression of other TJ protein but did reduce TJ formation as measured by transepithelial resistance and paracellular flux of dextran, enhance migration and invasion in in vitro assays, and increase lung colonization following intravenous injection. Knockdown of CLDN3 and CLDN4 increased total lung metastatic burden by 1.7-fold and 2.4-fold, respectively. Loss of either CLDN3 or CLDN4 resulted in down-regulation of E-cadherin mRNA and protein, increased inhibitory phosphorylation of glycogen synthase kinase-3β (GSK-3β), and activation of β-catenin pathway signaling as evidenced by increases in nuclear β-catenin, the dephosphorylated form of the protein, and transcriptional activity of β-catenin/T-cell factor (TCF). We conclude that both CLDN3 and CLDN4 mediate interactions with other cells in vivo that restrain growth and metastatic potential by sustaining expression of E-cadherin and limiting β-catenin signaling.

The membrane protein claudin-3 (CLDN3) is critical for the formation and maintenance of tight junction and its high expression has been implicated in dictating malignant progression in various cancers. However, the post-translational modification of CLDN3 and its biological function remains poorly understood. Here, we report that CLDN3 is positively correlated with ovarian cancer progression both in vitro and in vivo. Of interest, CLDN3 undergoes S -palmitoylation on three juxtamembrane cysteine residues, which contribute to the accurate plasma membrane localization and protein stability of CLDN3. Moreover, the deprivation of S -palmitoylation in CLDN3 significantly abolishes its tumorigenic promotion effect in ovarian cancer cells. By utilizing the co-immunoprecipitation assay, we further identify ZDHHC12 as a CLDN3-targating palmitoyltransferase from 23 ZDHHC family proteins. Furthermore, the knockdown of ZDHHC12 also significantly inhibits CLDN3 accurate membrane localization, protein stability and ovarian cancer cells tumorigenesis. Thus, our work reveals S -palmitoylation as a novel regulatory mechanism that modulates CLDN3 function, which implies that targeting ZDHHC12-mediated CLDN3 S -palmitoylation might be a potential strategy for ovarian cancer therapy. ZDHHC12-mediated S -palmitoylation promotes the cell membrane localization of CLDN3 and maintains its stability in ovarian cancer cells, contributing to the oncoprotein function of CLDN3. When ZDHHC12 was knocked down, CLDN3 was insufficiently S -palmitoylated leading to intracellular distribution and preference to degradation, which berried tumor growth. Image 1 [ABSTRACT FROM AUTHOR]

The present study investigated the protective effects of emodin on intestinal epithelial tight junction (TJ) barrier integrity in cecal ligation and puncture (CLP)-induced septic rats and its possible mechanisms of action. Healthy male Sprague-Dawley rats were randomly divided into three groups (n=20 per group): Sham group, CLP group and CLP + emodin group. Animals were sacrificed at 12 and 24 h after the model was established. Abdominal aortic blood and specimens of the ileum were harvested for analysis. The histopathological changes in intestinal mucosa and the ultrastructures of intestinal epithelial cells were investigated using light microscopy and transmission electron microscopy. The integrity of the intestinal barrier was assessed by examining plasma diamine oxidase (DAO) levels and the ratio of urine lactulose to mannitol (L/M). The levels of the intestinal TJ proteins claudin-3, zonula occludens (ZO)-1 and occludin were detected using immunohistochemistry, western blotting and reverse transcription-quantitative PCR. The results showed that the pathological damage to intestinal mucosa and the intestinal tissue injury score in the CLP + emodin group were significantly reduced compared to those of the CLP group, and the differences were more obvious at 24 h compared with 12 h. DAO activity and the L/M ratio in the emodin pre-treatment group decreased significantly at 24 h compared with the CLP groups. The protein and mRNA levels of the TJ proteins claudin-3, ZO-1 and occludin in the emodin pre-treatment groups at 12 and 24 h were increased, while occludin mRNA level was found to be decreased compared with the CLP groups. The present study suggested that emodin may significantly reduce the damage to the intestinal epithelial barrier in sepsis, inhibit intestinal barrier permeability and protect intestinal barrier integrity. Emodin may protect intestinal barrier integrity by elevating expression levels of the TJ proteins claudin-3, ZO-1 and occludin in CLP rats. [ABSTRACT FROM AUTHOR]

Purpose: Claudins as the major components of tight junctions are important in maintaining cell-cell integrity and thus function as a barrier. Dysregulation of the claudins is often associated with loss of the epithelial phenotype, a process called epithelial-mesenchymal transition (EMT), which most often results in gain of migrative and invasive properties. However, the role of claudins in the endometrium or endometriosis has only rarely been examined.Methods: In this study, we investigated localization of claudin-2 and claudin-3 in the eutopic and ectopic endometrium with immunohistochemistry. A detailed quantification with HSCORE was performed for claudin-2 and claudin-3 in endometrium without endometriosis and in cases with endometriosis compared to the three endometriotic entities: peritoneal, ovarian, and deep-infiltrating endometriosis.Results: We found a preferential localization of both claudins in the glandular and the luminal epithelial cells in the endometrium with and without endometriosis. Quantification of localization of both claudins showed no differences in eutopic endometrium of control cases compared to cases with endometriosis. Furthermore, both claudins are localized highly similar in the ectopic compared to the eutopic endometrium, which is in clear contrast to previously published data for claudin-3.Conclusion: From our results, we conclude that localization of claudin-2 and claudin-3 is highly stable in eutopic and ectopic endometrium without any loss of the epithelial phenotype and thus do not contribute to the pathogenesis of endometriosis. [ABSTRACT FROM AUTHOR]

Our aim was to study the association of endothelial dysfunction biomarkers with cirrhosis manifestations, bacterial translocation, and gut microbiota taxa. The fecal microbiome was assessed using 16S rRNA gene sequencing. Plasma levels of nitrite, big endothelin-1, asymmetric dimethylarginine (ADMA), presepsin, and claudin were measured as biomarkers of endothelial dysfunction, bacterial translocation, and intestinal barrier dysfunction. An echocardiography with simultaneous determination of blood pressure and heart rate was performed to evaluate hemodynamic parameters. Presepsin, claudin 3, nitrite, and ADMA levels were higher in cirrhosis patients than in controls. Elevated nitrite levels were associated with high levels of presepsin and claudin 3, the development of hemodynamic circulation, hypoalbuminemia, grade 2-3 ascites, overt hepatic encephalopathy, high mean pulmonary artery pressure, increased abundance of Proteobacteria and Erysipelatoclostridium , and decreased abundance of Oscillospiraceae , Subdoligranulum , Rikenellaceae , Acidaminococcaceae , Christensenellaceae , and Anaerovoracaceae . Elevated ADMA levels were associated with higher Child-Pugh scores, lower serum sodium levels, hypoalbuminemia, grade 2-3 ascites, milder esophageal varices, overt hepatic encephalopathy, lower mean pulmonary artery pressure, and low abundance of Erysipelotrichia and Erysipelatoclostridiaceae . High big endothelin-1 levels were associated with high levels of presepsin and sodium, low levels of fibrinogen and cholesterol, hypocoagulation, increased Bilophila and Coprobacillus abundances, and decreased Alloprevotella abundance.

Objective: Claudin family of proteins has been shown to be overexpressed in various cancers. We aimed to investigate one member of this family, the Claudin-3 expressions in prostate tissue and evaluate its utility as a diagnostic marker for prostatic adenocarcinoma. Material and Method: A total number of 50 cases of prostatic adenocarcinoma were reviewed from the files of M.H Ankara Dışkapı Research and Training Hospital. One paraffin block was selected for each case. For separate immunohistochemical staining with Alpha-methylacyl-CoA racemase (AMACR) and Claudin-3, two slides were sectioned from each block. Prostatic carcinoma (PC), Benign gland, and High grade prostatic intraepithealial neoplasia (HGPIN) components in each slide were evaluated. Afterwards the intensity of stainings were scored on a scale of 0-2 seperately for each component. Results: After immunohistochemical evaluation, 94.1% of PC showed positivity with Claudin-3 whereas this value was 77.4% for AMACR. Furthermore in the areas of HGPIN, the positivity rates with Claudin-3 was also higher than those of AMACR (p <0.005). Conclusion: In statistical analysis, Claudin-3 appeared to be a reliable immunohistochemical marker for PC at least as much as AMACR. We think that our findings strongly suggest the use of Claudin-3 as an alternative for AMACR in the routine tissue diagnosis of PC. [ABSTRACT FROM AUTHOR]

Various genomic and epigenetic modifications that occur during the development of cancer act as potential biomarkers for early diagnosis and treatment. Previous studies have demonstrated abnormal expression of the claudin (CLDN) tight junction (TJ) proteins in numerous types of human cancer. Reverse transcription-quantitative polymerase chain reaction and western blotting were employed to investigate variations in the expression of the CLDN TJ proteins in laryngeal non-neoplastic tissues and laryngeal squamous carcinoma tissues. It was revealed that CLDN2, CLDN4, CLDN5, CLDN6, CLDN9, CLDN11 and CLDN12 were undetectable in laryngeal squamous carcinoma tissues and laryngeal non-neoplastic tissues. Additionally, CLDN10 was expressed in laryngeal squamous carcinoma tissues and laryngeal non-neoplastic tissues; however, no significant difference was reported. Conversely, the expression levels of CLDN1 and CLDN7 mRNA and protein were downregulated in laryngeal squamous carcinoma tissues compared with in adjacent non-neoplastic tissues, whereas those of CLDN3 and CLDN8 were upregulated. A total of 80 samples of laryngeal squamous carcinoma and non-neoplastic tissues were analyzed for the expression of CLDN1, −3, −7 and −8 via streptavidin-peroxidase immunohistochemical staining. It was revealed that the expression levels of CLDN1 and CLDN7 were downregulated in laryngeal squamous carcinoma tissues compared with in non-neoplastic mucosal tissues, whereas those of CLDN3 and CLDN8 were upregulated. Furthermore, the associations between CLDN expression and the clinicopathological factors of patients were analyzed. The expression levels of CLDN3 and CLDN7 were reported to be associated with distant metastasis and serve as potential predictors of poor prognosis. In conclusion, the findings of the present study demonstrated that the expression levels of CLDN1, −3, −7 and −8 varied between laryngeal squamous carcinoma tissues and non-neoplastic tissues. The expression levels of these CLDNs may be useful molecular markers for the diagnosis of laryngeal carcinoma, and determining the metastasis and prognosis of this disease. [ABSTRACT FROM AUTHOR]

Expression and significance of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and Claudin-3 in the blood of patients with prostate cancer [prostate cancer (PCa)] were investigated. Retrospective analysis of 84 cases of PCa patients confirmed by pathological diagnosis were studied, as the experiment group. Moreover, the physical examination data of 84 healthy volunteers examined in the Affiliated Hospital of Beihua University were the control group. The expression levels of blood in the PTEN and Claudin-3 of both the experiment group and the control group were determined by enzyme-linked immunosorbent assay. According to the blood expression in PTEN and Claudin-3 between both the experiment group and the control group, the test value of the ROC curve in PTEN and Claudin-3 were detected by both single detection and joint detection. The expression levels of PTEN in the experiment group were significantly lower than the control group (P<0.05). The expression levels of Claudin-3 were higher in the experiment group than the control group (P<0.01). The expression levels of PTEN and Claudin-3 in the experiment group were significantly associated with the distant metastasis of cancer cells, preoperative prostate-specific antigen levels, tumor diameter and pathological stages (P<0.01). The expression levels of PTEN in the pathological stage of T1-T2 group was lower than that of the T3-T4 group (P<0.01). The expression levels of PTEN and Claudin-3 are closely related to the distant metastasis of cancer cells, preoperative prostate-specific antigen level, tumor diameter and pathological stage. Combined detection of both PTEN and Claudin-3 can improve the specificity levels of PCa for diagnosis and has an important diagnostic value for PCa. It can be used as a biological indicator for PCa diagnosis, disease severity analysis and efficacy evaluation. [ABSTRACT FROM AUTHOR]

Background: M cells and intestinal tight junction proteins (TJPs) are important components of intestinal barrier which is compromised by high fat diet (HFD). Objective: To determine the effect of HFD on M cells and TJPs of intestinal villi of rats. Materials and Methods: Four weeks old, twenty male Wistar rats were divided into control (n = 10) and HFD (n = 10) groups. After 6 weeks, rats were sacrificed, ileum segments and feces were collected. Immunohistochemical staining and fecal calprotectin (FCP) level were measured. Data were presented as mean ± SD. Ap value of < 0.05 was considered as significant. Results: As compared to the control, M cell expression in the villi was significantly higher in HFD group (1.625 ± 0.518 vs 2.3 ± 0.458, p = 0.045). Claudin-3 was highly expressed in the villi of both groups. As compared to the control, claudin-4 expression in the villi was significantly lower in HFD group (1.975 ± 0.670 vs 1.55 ± 0.597, p = 0.015). As compared to the control, occludin expression in the villi was reduced but not significantly in HFD group (1.5 ± 0.592 vs 1.45 ± 0.497, p = 0.589). As compared to the control, FCP level was found significantly higher in HFD group (40.172 ± 4.0852 vs 49.058 ± 1.174, p = 0.016). Conclusion: HFD consumption for 6 weeks caused higher expression of M cell, no significant changes of claudin-3 expression, reduced claudin-4 and occludin expression in the villi of male Wistar rats which were associated with intestinal inflammation. [ABSTRACT FROM AUTHOR]

Diagnosing acute rejection after intestinal transplantation currently heavily relies on histopathological analysis of graft biopsies. However, the invasive risks associated with ileoscopic examination and the inaccessibility for biopsy after ileostomy closure hinder real-time detection of rejection responses. Molecules comprising the intestinal barrier have been identified as physiological and molecular biomarkers for various bowel conditions and systemic diseases. To investigate the potential of barrier function-related molecules in diagnosing rejection after intestinal transplantation, plasma samples were collected longitudinally from transplant recipients. The samples were categorized into "indeterminate for rejection (IND)" and "acute rejection (AR)" groups based on clinical diagnoses at each time point. The longitudinal association between plasma levels of these barrier function-related molecules and acute rejection was analyzed using the generalized estimating equations (GEE) method. Logistic GEE models revealed that plasma levels of claudin-3, occludin, sIgA, and zonulin were independent variables correlated with the clinical diagnosis of acute rejection. The subsequent prediction model demonstrated moderate ability in discriminating between IND and AR samples, with a sensitivity of 76.0%, specificity of 89.2%, and accuracy of 84.6%. In conclusion, monitoring plasma levels of claudin-3, occludin, sIgA, and zonulin shows great potential in aiding the diagnosis of acute rejection after intestinal transplantation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chen, Tseng, Chen and Tsai.)

Objective To investigate the effect of salidroside on intestinal mucosal immune status in rats under compound stress of hypoxia and training (HTCS) and the mechanism. Methods SD rats were randomly divided into HTCS model group (model), placebo group (placebo) and salidroside group (salidro). Model group received no intervention, and placebo and salidro group received intraperitoneal injection of normal saline and salidroside, respectively. Then, ileum tissue of rats were collected and the intestinal damage was assayed by HE staining and Chiu scores. Intestinal permeability indices, including serum D-diamine oxidase (DAO), D-lactic acid (DLA) and endotoxin (END) and secretory immunoglobulin A (sIgA) of intestinal tissue were detected by ELISA. T lymphocyte subsets of intestinal tissue were detected by flow cytometry. Expression of tight junction molecules, including ZO-1, Claudin-3, occluding, were detected by PCR and western blot. Activation of TLR4/NF-κB signaling pathway was detected by Western blot analysis. Results Compared with model group and placebo group, salidro group had the decreased intestinal mucosal injury and low Chiu score, and the level of intestinal permeability indices including serum DAO, DLA and END fell off. CD4 + T cell percentage, CD4 + /CD8 + ratio and sIgA level were went up, while CD8 + T cell percentage was went down. mRNA and the level of protein expressions of ZO-1, claudin-3 and occludin increased, while activation of TLR4/NF-κB signaling pathway was inhibited. Conclusion Salidroside can alleviate the intestinal barrier injury and improve intestinal mucosal immune status of rats under compound stress of hypoxia and training via inhibiting TLR4/NF-κB signalling pathway.

Objective To observe the expression of Snail and Claudin-3 in the primary hepatocellular carcinoma tissues and to explore their clinical significance. Methods The expression of Snail and Claudin-3 in 85 cases of hepatocellular carcinoma tissues and paired adjacent normal hepatic tissues were examined by immunohistochemical method. The correlation of Snail and Claudin-3 expression with their clinicopathological characteristics was analyzed. The relationship between expression of Snail and Claudin-3 in the hepatocellular carcinoma tissues was tested by Spearmans rank correlation coefficient. Kaplan-Meier curve was applied to evaluate the prognosis. Results The positive rates of Snail in the hepatocellular carcinoma tissues and adjacent hepatic tissues were 69.41% (59/85) and 36.47% (31/85), respectively; the positive rates of Claudin-3 in the hepatocellular carcinoma tissues and adjacent hepatic tissues were 47.06% (40/85) and 78.82% (40/85), respectively; therefore, statistically significant differences were found between these two kinds of tissues (both P <0.05). The expression of Snail and Claudin-3 in the hepatocellular carcinoma tissues was closely related to TNM stage and microvascular invasion (all P < 0.05), hut was not related to age, gender, tumor size, or hepatocirrhosis (all P >0.05). The expression of Snail and Claudin-3 in the hepatocellular carcinoma tissues was negatively correlated (r = -0.551, P = 0.000). The follow-up results indicated that the total survival rate and average survival time of patients with positive expression of Snail were significantly shorter than those of patients with negative expression, while the total survival rate and average survival time of patients with negative expression of Claudin-3 were significantly shorter than those of patients with positive expression (both P <0.05). Conclusion In the hepatocellular carcinoma tissues, the expression of Snail is abnormally up-graded and Claudin-3 is down-graded, and the change of their expression may play a role in the occurrence and malignant development of hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]

Claudins are members of a large family of transmembrane proteins, which are essential for the formation of tight junctions and have a significant effect on the biological behavior of tumor progression. Previous studies have demonstrated that several claudins show aberrant expression patterns in numerous types of cancer. The present study investigated the expression and localization of claudin-3 and claudin-7 in human colorectal adenocarcinoma cell lines and tissues. The protein expression levels of claudin-3 and claudin-7 were determined using immunocytochemical and immunohistochemical staining. Claudin-3, but not claudin-7, exhibited nuclear localization in the human colorectal adenocarcinoma Caco-2 and SW620 cell lines. Surgically resected colorectal adenocarcinoma tissue specimens were obtained, and the associations between the expression of claudin-3 or claudin-7 and various clinicopathological parameters were analyzed. The membranous expression rates of claudin-3 and claudin-7 were 58.0 and 50.0%, while their nuclear expression rates were 22.0 and 2.0%, respectively. The membranous expression of claudin-3 and claudin-7 was not associated with any clinicopathological factors, whereas the nuclear expression of claudin-3 was associated with histological type and was significantly increased in colorectal mucinous adenocarcinomas compared with that in well- to moderately-differentiated colorectal adenocarcinomas (P<0.01). However, no associations were observed between the nuclear expression of claudin-7 and any clinicopathological parameter. In conclusion, the nuclear expression of claudin-3 in colorectal mucinous adenocarcinoma may be involved in the biological transformation of tumors. The results from the present study indicated that claudin-3 is an important protein associated with histological type and has potential as a prognostic marker. Although the mechanisms underlying the nuclear localization of claudin-3 in tumorigenesis have not yet been elucidated in detail, the present results indicated the potential of claudin-3 as a histopathological biomarker for colorectal adenocarcinomas. [ABSTRACT FROM AUTHOR]

Defects in intestinal epithelial tight junctions (TJs) allow paracellular permeation of noxious luminal antigens and are important pathogenic factors in inflammatory bowel disease (IBD). We show that alpha-tocopherylquinone (TQ), a quinone-structured oxidation product of vitamin E, consistently enhances the intestinal TJ barrier by increasing barrier-forming claudin-3 (CLDN3) and reducing channel-forming CLDN2 in Caco-2 cell monolayers (in vitro), mouse models (in vivo), and surgically resected human colons (ex vivo). TQ reduces colonic permeability and ameliorates colitis symptoms in multiple colitis models. TQ, bifunctionally, activates both aryl hydrocarbon receptor (AhR) and nuclear factor erythroid 2-related factor 2 (Nrf2) pathways. Genetic deletion studies reveal that TQ-induced AhR activation transcriptionally increases CLDN3 via xenobiotic response element (XRE) in the CLDN3 promoter. Conversely, TQ suppresses CLDN2 expression via Nrf2-mediated STAT3 inhibition. TQ offers a naturally occurring, non-toxic intervention for enhancement of the intestinal TJ barrier and adjunct therapeutics to treat intestinal inflammation. [Display omitted] • Alpha-tocopherylquinone (TQ) enhances intestinal tight junction (TJ) barrier • TQ increases barrier-forming CLDN3 expression via AhR • TQ reduces channel-forming CLDN2 via Nrf-mediated STAT3 inactivation • TQ ameliorates experimental colitis Ganapathy et al. show that alpha-tocopherylquinone reduces intestinal paracellular permeability via an AhR-mediated increase in tight junction barrier-forming CLDN3 and an Nrf2-mediated reduction in channel-forming CLDN2 expression. α-tocopherylquinone-mediated enhancement of the tight junction barrier is associated with amelioration of experimental colitis. [ABSTRACT FROM AUTHOR]