Vitamin D regulates claudin-2 and claudin-4 expression in active ulcerative colitis by p-Stat-6 and Smad-7 signaling

Domazetovic, Vladana; Iantomasi, Teresa; Bonanomi, Andrea; Stio, Maria

doi:10.1007/s00384-020-03576-0

Cited by 29 publications

(23 citation statements)

References 46 publications

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“…Redistribution of occludin and of the sealing TJ protein claudin-4 induced by C. jejuni contributes to barrier dysfunction by opening the paracellular leak pathway to ions, water, and macromolecules, so that antigen influx activates immune cells and triggers cytokine release, which further compromises the epithelial barrier and results in a 'leaky gut'. In our in vitro model, VD restored, at least in part, the expression and normal distribution of the TJ proteins, as reported in TNF-α-stimulated Caco-2 cells [25] and in T84 cells or in colonic biopsies from patients with ulcerative colitis [32].…”

Section: Effect Of C Jejuni and Vitamin D On Tight Junction Protein Expression Localization And Apoptosis Inductionsupporting

confidence: 80%

Vitamin D Reverses Disruption of Gut Epithelial Barrier Function Caused by Campylobacter jejuni

Sá

Backert

Nattramilarasu

et al. 2021

IJMS

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Infections by the zoonotic foodborne bacterium Campylobacter jejuni (C. jejuni) are among the most frequent causes of bacterial gastroenteritis worldwide. The aim was to evaluate the relationship between epithelial barrier disruption, mucosal immune activation, and vitamin D (VD) treatment during C. jejuni infection, using intestinal epithelial cells and mouse models focused on the interaction of C. jejuni with the VD signaling pathway and VD treatment to improve C. jejuni-induced barrier dysfunction. Our RNA-Seq data from campylobacteriosis patients demonstrate inhibition of VD receptor (VDR) downstream targets, consistent with suppression of immune function. Barrier-preserving effects of VD addition were identified in C. jejuni-infected epithelial cells and IL-10−/− mice. Furthermore, interference of C. jejuni with the VDR pathway was shown via VDR/retinoid X receptor (RXR) interaction. Paracellular leakiness of infected epithelia correlated with tight junction (TJ) protein redistribution off the TJ domain and apoptosis induction. Supplementation with VD reversed barrier impairment and prevented inhibition of the VDR pathway, as shown by restoration of transepithelial electrical resistance and fluorescein (332 Da) permeability. We conclude that VD treatment restores gut epithelial barrier functionality and decreases bacterial transmigration and might, therefore, be a promising compound for C. jejuni treatment in humans and animals.

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Section: Effect Of C Jejuni and Vitamin D On Tight Junction Protein Expression Localization And Apoptosis Inductionsupporting

confidence: 80%

Vitamin D Reverses Disruption of Gut Epithelial Barrier Function Caused by Campylobacter jejuni

Sá

Backert

Nattramilarasu

et al. 2021

IJMS

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“…Interestingly expression of either Claudin-2 or Occludinn is regulated by a separate mode of proteins and small molecule intermediates endogenously found in the intestinal epithelial cells. Vitamin D, transcription factors such as SNAIL and GRHL2 have been shown to be effectively modulating the expression of these proteins [ 35 , 66 , 67 , 68 ]. It would be interesting to study the mechanisms of AG in controlling the transcription factors both at the intestinal epithelium barrier and the BBB to know for certain the mechanisms involved in its effectiveness.…”

Section: Discussionmentioning

confidence: 99%

Andrographolide Attenuates Gut-Brain-Axis Associated Pathology in Gulf War Illness by Modulating Bacteriome-Virome Associated Inflammation and Microglia-Neuron Proinflammatory Crosstalk

et al. 2021

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Gulf War Illness (GWI) is a chronic multi-symptomatic illness that is associated with fatigue, pain, cognitive deficits, and gastrointestinal disturbances and presents a significant challenge to treat in clinics. Our previous studies show a role of an altered Gut–Brain axis pathology in disease development and symptom persistence in GWI. The present study utilizes a mouse model of GWI to study the role of a labdane diterpenoid andrographolide (AG) to attenuate the Gut–Brain axis-linked pathology. Results showed that AG treatment in mice (100 mg/kg) via oral gavage restored bacteriome alterations, significantly increased probiotic bacteria Akkermansia, Lachnospiraceae, and Bifidobacterium, the genera that are known to aid in preserving gut and immune health. AG also corrected an altered virome with significant decreases in virome families Siphoviridae and Myoviridae known to be associated with gastrointestinal pathology. AG treatment significantly restored tight junction proteins that correlated well with decreased intestinal proinflammatory mediators IL-1β and IL-6 release. AG treatment could restore Claudin-5 levels, crucial for maintaining the BBB integrity. Notably, AG could decrease microglial activation and increase neurotrophic factor BDNF, the key to neurogenesis. Mechanistically, microglial conditioned medium generated from IL-6 stimulation with or without AG in a concentration similar to circulating levels found in the GWI mouse model and co-incubated with neuronal cells in vitro, decreased Tau phosphorylation and neuronal apoptosis. In conclusion, we show that AG treatment mitigated the Gut–Brain-Axis associated pathology in GWI and may be considered as a potential therapeutic avenue for the much-needed bench to bedside strategies in GWI.

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“…Additionally, some vitamins can regulate the expression of claudins. For example, vitamin D can regulate claudin-2, -4 and -15 protein levels, suggesting that vitamin D administration to ulcerative colitis (UC) patients could be a useful therapeutic intervention to relieve intestinal inflammation and prevent CAC ( 154 , 155 ).…”

Section: The Complexity Of Claudins In Cancermentioning

confidence: 99%

Context-Dependent Roles of Claudins in Tumorigenesis

2021

Front. Oncol.

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The barrier and fence functions of the claudin protein family are fundamental to tissue integrity and human health. Increasing evidence has linked claudins to signal transduction and tumorigenesis. The expression of claudins is frequently dysregulated in the context of neoplastic transformation. Studies have uncovered that claudins engage in nearly all aspects of tumor biology and steps of tumor development, suggesting their promise as targets for treatment or biomarkers for diagnosis and prognosis. However, claudins can be either tumor promoters or tumor suppressors depending on the context, which emphasizes the importance of taking various factors, including organ type, environmental context and genetic confounders, into account when studying the biological functions and targeting of claudins in cancer. This review discusses the complicated roles and intrinsic and extrinsic determinants of the context-specific effects of claudins in cancer.

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Vitamin D regulates claudin-2 and claudin-4 expression in active ulcerative colitis by p-Stat-6 and Smad-7 signaling

Cited by 29 publications

References 46 publications

Vitamin D Reverses Disruption of Gut Epithelial Barrier Function Caused by Campylobacter jejuni

Vitamin D Reverses Disruption of Gut Epithelial Barrier Function Caused by Campylobacter jejuni

Andrographolide Attenuates Gut-Brain-Axis Associated Pathology in Gulf War Illness by Modulating Bacteriome-Virome Associated Inflammation and Microglia-Neuron Proinflammatory Crosstalk

Context-Dependent Roles of Claudins in Tumorigenesis

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