Alpha-tocopherylquinone differentially modulates claudins to enhance intestinal epithelial tight junction barrier via AhR and Nrf2 pathways

Ganapathy, Ashwinkumar Subramenium; Saha, Kushal; Wang, Alexandra; Arumugam, Priya; Viszwapriya, Dharmaprakash; Yochum, Gregory S.; Koltun, Walter A.; Nighot, Meghali; Perdew, Gary H.; Thompson, Todd A.; Ma, Thomas; Nighot, Prashant K.

doi:10.1016/j.celrep.2023.112705

Cited by 13 publications

(7 citation statements)

References 70 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In our previous studies, we have observed that TQ enhances the intestinal epithelial tight junction barrier in an AhR-dependent mechanism and ameliorates disease activity and inflammation in various models of experimental colitis 25 . The role of TQ in the regulation of intestinal immune responses is not known.…”

Section: Resultsmentioning

confidence: 96%

“…As functional interactions between NFκB and Stat-3 in immune cells control the production of pro-inflammatory cytokines 32 , and our previous studies also showed inhibition of Stat-3 by TQ in the intestinal epithelium 25 , we also assessed the activation of the Stat-3 in U937 cells in the presence and absence of TQ. TQ significantly inhibited the LPS-induced phosphorylation and hence activation of Stat-3 ( Figs.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Alpha-tocopherylquinone-mediated activation of the Aryl Hydrocarbon Receptor regulates the production of inflammation-inducing cytokines and ameliorates intestinal inflammation

Saha,

Subramenium Ganapathy,

Wang

et al. 2023

Mucosal Immunology

Self Cite

View full text Add to dashboard Cite

Section: Resultsmentioning

confidence: 96%

Section: Resultsmentioning

confidence: 99%

Alpha-tocopherylquinone-mediated activation of the Aryl Hydrocarbon Receptor regulates the production of inflammation-inducing cytokines and ameliorates intestinal inflammation

Saha,

Subramenium Ganapathy,

Wang

et al. 2023

Mucosal Immunology

Self Cite

View full text Add to dashboard Cite

“… 19 Other studies have shown similar positive association of CLDN3 expression with gut barrier integrity. 38 These data, when combined with the fact that CLDN3 expression is markedly suppressed in IBD patients and murine models of colitis, emphasize the significance of promoting CLDN3 in improving the prognosis of IBD.…”

Section: Discussionmentioning

confidence: 93%

Loss of claudin-3 expression increases colitis risk by promoting Gut Dysbiosis

Ahmad,

Kumar,

Thapa

et al. 2023

Gut Microbes

View full text Add to dashboard Cite

Dysregulation of both the gut barrier and microbiota (dysbiosis) promotes susceptibility to and severity of Inflammatory Bowel Diseases (IBD). Leaky gut and dysbiosis often coexist; however, potential interdependence and molecular regulation are not well understood. Robust expression of claudin-3 (CLDN3) characterizes the gut epithelium, and studies have demonstrated a positive association between CLDN3 expression and gut barrier maturity and integrity, including in response to probiotics. However, the exact status and causal role of CLDN3 in IBD and regulation of gut dysbiosis remain unknown. Analysis of mouse and human IBD cohorts helped examine CLDN3 expression in IBD. The causal role was determined by modeling CLDN3 loss of expression during experimental colitis. 16S sequencing and in silico analysis helped examine gut microbiota diversity between Cldn3 KO and WT mice and potential host metabolic responses. Fecal microbiota transplant (FMT) studies were performed to assess the role of gut dysbiosis in the increased susceptibility of Cldn3 KO mice to colitis. A significant decrease in CLDN3 expression characterized IBD and CLDN3 loss of expression promoted colitis. 16S sequencing analysis suggested gut microbiota changes in Cldn3 KO mice that were capable of modulating fatty acid metabolism and oxidative stress response. FMT from naïve Cldn3 KO mice promoted colitis susceptibility in recipient germ-free mice (GFM) compared with GFM-receiving microbiota from WT mice. Our data demonstrate a critical role of CLDN3 in maintaining normal gut microbiota and inflammatory responses, which can be harnessed to develop novel therapeutic opportunities for patients with IBD.

show abstract

“…Research on CLDN2 has primarily focused on gastrointestinal diseases, due to its role as a member of the tight junction protein family, prompting extensive investigation into its role about the intestinal barrier ( Beggs et al, 2023 ; Ganapathy et al, 2023 ; Rini et al, 2023 ). Numerous studies have progressively affirmed its association with inflammatory bowel diseases ( Raju et al, 2020 ; Ahmad et al, 2023 ; Alghamdi and Al-Zahrani, 2023 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of claudin-2 as a promising biomarker for early diagnosis of pre-diabetes

Songtao,

Fangyu,

Jie

et al. 2024

Front. Pharmacol.

View full text Add to dashboard Cite

Introduction: Pre-diabetes, a high-risk metabolic state, is situated between normal glucose homeostasis and diabetes. Early identification of pre-diabetes offers opportunities for intervention and diabetes reversal, highlighting the crucial need to investigate reliable biomarkers for this condition.Methods: We conducted an in-depth bioinformatics analysis of clinical samples from non-diabetic (ND), impaired glucose tolerance (IGT), and type 2 diabetes mellitus (T2DM) categories within the GSE164416 dataset. Thereafter the HFD and STZ treated mice were used for validation.Results: This analysis identified several codifferentially expressed genes (Co-DEGs) for IGT and T2DM, including CFB, TSHR, VNN2, APOC1, CLDN2, SLPI, LCN2, CXCL17, FAIM2, and REG3A. Validation of these genes and the determination of ROC curves were performed using the GSE76895 dataset. Thereafter, CLDN2 was selected for further verification. Gene expression analysis and immunofluorescence analysis revealed a significant upregulation of CLDN2 expression in the pancreas islets of mice in the high-fat diet and T2DM groups compared to the control group. Similarly, serum level of CLDN2 in patients with IGT and T2DM were significantly higher than those in the healthy group.Discussion: These results suggest that CLDN2 can serve as a novel biomarker for pre-diabetes, providing a new direction for future research in the prevention of type 2 diabetes.

show abstract

Alpha-tocopherylquinone differentially modulates claudins to enhance intestinal epithelial tight junction barrier via AhR and Nrf2 pathways

Cited by 13 publications

References 70 publications

Alpha-tocopherylquinone-mediated activation of the Aryl Hydrocarbon Receptor regulates the production of inflammation-inducing cytokines and ameliorates intestinal inflammation

Alpha-tocopherylquinone-mediated activation of the Aryl Hydrocarbon Receptor regulates the production of inflammation-inducing cytokines and ameliorates intestinal inflammation

Loss of claudin-3 expression increases colitis risk by promoting Gut Dysbiosis

Identification of claudin-2 as a promising biomarker for early diagnosis of pre-diabetes

Contact Info

Product

Resources

About