Evidence map›Paper›PMID 37393618›Full record

ArticleCell reports2023

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

Ashwinkumar Subramenium Ganapathy, Kushal Saha, Alexandra Wang, Priya Arumugam, Viszwapriya Dharmaprakash, Gregory Yochum, Walter Koltun, Meghali Nighot, Gary Perdew, Todd A Thompson and 2 more

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
4.5field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

28 citing papers in PubMed, 37 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 3 institutions in 1 country.

Ashwinkumar Subramenium GanapathyDivision of Gastroenterology and Hepatology, Department of Medicine, Pennsylvania State College of Medicine, Hershey, PA 17033, USA.
Kushal SahaDivision of Gastroenterology and Hepatology, Department of Medicine, Pennsylvania State College of Medicine, Hershey, PA 17033, USA.
Alexandra WangDivision of Gastroenterology and Hepatology, Department of Medicine, Pennsylvania State College of Medicine, Hershey, PA 17033, USA.
Priya ArumugamDivision of Gastroenterology and Hepatology, Department of Medicine, Pennsylvania State College of Medicine, Hershey, PA 17033, USA.
Viszwapriya DharmaprakashDivision of Gastroenterology and Hepatology, Department of Medicine, Pennsylvania State College of Medicine, Hershey, PA 17033, USA.
Gregory YochumDivision of Colon and Rectal Surgery, Department of Surgery, Pennsylvania State College of Medicine, Hershey, PA 17033, USA.
Walter KoltunDivision of Colon and Rectal Surgery, Department of Surgery, Pennsylvania State College of Medicine, Hershey, PA 17033, USA.
Meghali NighotDivision of Gastroenterology and Hepatology, Department of Medicine, Pennsylvania State College of Medicine, Hershey, PA 17033, USA.
Gary PerdewDepartment of Veterinary and Biomedical Sciences and the Center for Molecular Toxicology and Carcinogenesis, The Pennsylvania State University, University Park, PA 16802, USA.
Todd A ThompsonUniversity of New Mexico College of Pharmacy, Albuquerque, NM 87131, USA.
Thomas MaDivision of Gastroenterology and Hepatology, Department of Medicine, Pennsylvania State College of Medicine, Hershey, PA 17033, USA.
Prashant NighotDivision of Gastroenterology and Hepatology, Department of Medicine, Pennsylvania State College of Medicine, Hershey, PA 17033, USA. Electronic address: pnighot@pennstatehealth.psu.edu.
Penn State Milton S. Hershey Medical Center · USPennsylvania State University · USUniversity of New Mexico · US

Funding

Activation of the Ah receptor and epithelial integrityR35ES028244 · NIEHS · PENNSYLVANIA STATE UNIVERSITY, THE · PI PERDEW, GARY H. · 2017 to 2024
$6.2M
Regulation of Intestinal Tight Junction Barrier and Inflammation by AutophagyR01DK114024 · NIDDK · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · PI NIGHOT, PRASHANT · 2017 to 2021
$1.8M
Role of the chloride channel ClC-2 in intestinal tight junction barrier recoveryK01DK100562 · NIDDK · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · PI NIGHOT, PRASHANT · 2014 to 2018
$684k
NIDDK NIH HHS K01 DK100562NIDDK NIH HHS R01 DK114024NIEHS NIH HHS R35 ES028244
6 · The paper itself

Abstract

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.

Indexed as

ClaudinsColitisAnimalsCaco-2 CellsHumansIntestinal MucosaMiceNF-E2-Related Factor 2PermeabilityReceptors, Aryl HydrocarbonTight JunctionsVitamin EClaudinsNF-E2-Related Factor 2Receptors, Aryl HydrocarbontocopherylquinoneVitamin Ealpha-tocopherylquinonearyl hydrocarbon receptorclaudin-2claudin-3CP: Cell biologyinflammatory bowel diseaseintestinal permeabilitytight junction

Identifiers

PMID37393618
PMCPMC10528852
OpenAlexW4382752900

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.