Evidence map›Paper›PMID 29208693›Full record

ArticlePhysiological reports2017

Dysregulation of junctional adhesion molecule-A contributes to ethanol-induced barrier disruption in intestinal epithelial cell monolayers.

Daniel M Chopyk, Pradeep Kumar, Reben Raeman, Yunshan Liu, Tekla Smith, Frank A Anania

Abstract read
In one paragraph

Article in Physiological reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

23 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
  3. Review
  4. Review
  5. Article
  6. Review
  7. Article
  8. Traditional and emergingAnimal nutrition (Zhongguo xu mu shou yi xue hui) · 2023
    Article
  9. Article
  10. Article
  11. Article
  12. The Immune System through the Lens of Alcohol Intake and Gut Microbiota.International journal of molecular sciences · 2021
    Review
  13. Review
  14. Review
  15. Review
  16. Review
  17. Western diet-induced increase in colonic bile acids compromises epithelial barrier in nonalcoholic steatohepatitis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020
    Article
  18. Article
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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

6 authors.

Daniel M ChopykDivision of Digestive Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia.ORCID http://orcid.org/0000-0003-4207-1360
Pradeep KumarDivision of Digestive Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia.ORCID http://orcid.org/0000-0002-6545-9555
Reben RaemanDivision of Digestive Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia.ORCID http://orcid.org/0000-0002-9589-0944
Yunshan LiuDivision of Digestive Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia.
Tekla SmithDivision of Digestive Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia.
Frank A AnaniaDivision of Digestive Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia.ORCID http://orcid.org/0000-0002-6718-5551

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM008169 · NIGMS · EMORY UNIVERSITY · PI GROSS, ROBERT E · 1987 to 2021
$20.3M
The Role of Leptin in Liver FibrogenesisR01DK062092 · NIDDK · UNIVERSITY OF MARYLAND BALTIMORE · PI ANANIA, FRANK A · 2003 to 2016
$3.9M
Defects in junctional adhesion molecule-A and Intestinal Permeability: Identification of Novel Mechanisms Driving Non-Alcoholic SteatohepatitisR01DK111678 · NIDDK · EMORY UNIVERSITY · PI CZAJA, MARK J · 2017 to 2020
$1.9M
Role of CD4 T cells in the pathogenesis of non-alcoholic steatohepatitisK01DK110264 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI RAEMAN, REBEN · 2017 to 2021
$702k
A pivotal role for junctional adhesion molecule-A in alcoholic liver injuryF31AA024960 · NIAAA · EMORY UNIVERSITY · PI CHOPYK, DANIEL MICHAEL · 2016 to 2018
$147k
Mechanisms of glucagon-like peptide 1 (GLP-1) in fatty liver diseaseI01BX001746 · VA · VETERANS HEALTH ADMINISTRATION · PI ANANIA, FRANK A · 2013 to 2016
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BLRD VA I01 BX001746NIAAA NIH HHS F31 AA024960NIDDK NIH HHS K01 DK110264NIDDK NIH HHS R01 DK062092NIDDK NIH HHS R01 DK111678NIGMS NIH HHS T32 GM008169
6 · The paper itself

Abstract

Alcohol consumption promotes loss of intestinal barrier function. However, mechanisms by which ethanol affects the tight junction (TJ), the cellular structure responsible for maintaining the gut epithelial barrier, are not well understood. Three classes of transmembrane proteins comprise TJs: occludin, claudins, and junctional adhesion molecules (JAMs). It has recently been postulated that JAM-A (F11R), the most abundant JAM expressed in intestinal epithelium, regulates "leak" pathway flux, a paracellular route for the nonselective permeation of large solutes. Since transluminal flux of many gut-derived antigens occurs through this pathway, we investigated the role of JAM-A in ethanol-induced disruption of the intestinal epithelial barrier. Using Caco-2 and SK-CO15 monolayers, we found that ethanol induced a dose- and time-dependent decrease in JAM-A protein expression to about 70% of baseline levels. Alcohol also reduced Ras-related protein 2 (Rap2) activity, and enhanced myosin light chain kinase (MLCK) activity, changes consistent with impaired JAM-A signaling. Stable overexpression and shRNA-mediated knockdown of JAM-A were employed to investigate the role of JAM-A in paracellular-mediated flux following alcohol exposure. The paracellular flux of 40-kDa fluorescein isothiocynate (FITC)-dextran following ethanol treatment was decreased by the overexpression of JAM-A; conversely, flux was enhanced by JAM-A knockdown. Thus, we conclude that ethanol-mediated control of JAM-A expression and function contributes to mechanisms by which this chemical induces intestinal epithelial leakiness.

Indexed as

AnimalsCaco-2 CellsCell Adhesion MoleculesEthanolHEK293 CellsHumansIntestinal AbsorptionIntestinal MucosaMaleMiceMice, Inbred C57BLMyosin Light Chainsrap GTP-Binding ProteinsReceptors, Cell SurfaceCell Adhesion MoleculesEthanolF11r protein, mouseMyosin Light ChainsRap2a protein, mouserap GTP-Binding ProteinsReceptors, Cell SurfaceCaco‐2ethanolintestinal epithelial barrierJunctional adhesion molecule‐Amyosin light chain kinaseRap2

Identifiers

PMID29208693
PMCPMC5727288

What OpenQuestion holds

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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.