Evidence map›Paper›PMID 31237689›Full record

ArticleAlcoholism, clinical and experimental research2019

Specifically Sized Hyaluronan (35 kDa) Prevents Ethanol-Induced Disruption of Epithelial Tight Junctions Through a layilin-Dependent Mechanism in Caco-2 Cells.

Damien A Bellos, Dhara Sharma, Megan R McMullen, Jeanette Wat, Paramananda Saikia, Carol A de la Motte, Laura E Nagy

Open access · greenAbstract read
In one paragraph

Article in Alcoholism, clinical and experimental research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.1field-weighted citation impact, top 23% 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

11 citing papers in PubMed, 11 citations in OpenAlex.

  1. Article
  2. Review
  3. 35k Da specific-sized hyaluronan ameliorates high-fat diet-induced liver injury in murine model of moderate obesity.Matrix biology : journal of the International Society for Matrix Biology · 2025
    Article
  4. Review
  5. Article
  6. Review
  7. Article
  8. Article
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  10. Article
  11. Pathogenesis of Alcohol-Associated Liver Disease.Journal of clinical and experimental hepatology
    Review
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

7 authors at 1 institution in 1 country.

Damien A BellosDepartment of Inflammation and Immunity, Center for Liver Disease Research, Cleveland Clinic, Cleveland, Ohio.
Dhara SharmaDepartment of Inflammation and Immunity, Center for Liver Disease Research, Cleveland Clinic, Cleveland, Ohio.
Megan R McMullenDepartment of Inflammation and Immunity, Center for Liver Disease Research, Cleveland Clinic, Cleveland, Ohio.
Jeanette WatDepartment of Inflammation and Immunity, Center for Liver Disease Research, Cleveland Clinic, Cleveland, Ohio.
Paramananda SaikiaDepartment of Inflammation and Immunity, Center for Liver Disease Research, Cleveland Clinic, Cleveland, Ohio.
Carol A de la MotteDepartment of Inflammation and Immunity, Center for Liver Disease Research, Cleveland Clinic, Cleveland, Ohio.
Laura E NagyDepartment of Inflammation and Immunity, Center for Liver Disease Research, Cleveland Clinic, Cleveland, Ohio.ORCID 0000-0002-0580-2809
Cleveland Clinic · US

Funding

CTSA INFRASTRUCTURE FOR PEDIATRIC RESEARCHUL1RR024989 · NCRR · CASE WESTERN RESERVE UNIVERSITY · PI DAVIS, PAMELA B · 2007 to 2011
$53.7M
Clinical and Translational Science Collaborative of ClevelandUL1TR002548 · NCATS · CASE WESTERN RESERVE UNIVERSITY · PI MCCOMSEY, GRACE A · 2018 to 2022
$35.5M
Project Two - Exercise Training Decreases Alcohol Drinking by an FGF21-Dependent MechanismP50AA024333 · NIAAA · CLEVELAND CLINIC LERNER COM-CWRU · PI LAURA E. NAGY · 2016 to 2026
$19.6M
VERSICAN PROTEOLYSIS AND REGULATION OF VASCULAR SMOOTH MUSCLEP01HL107147 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI DE LA MOTTE, CAROL A. · 2011 to 2017
$16.1M
Specific-sized hyaluronan: a dual targeted therapy for ALDR01AA026764 · NIAAA · CLEVELAND CLINIC LERNER COM-CWRU · PI NAGY, LAURA E. · 2018 to 2022
$2.1M
Spinning Disk Confocoal MicroscopeS10RR026820 · NCRR · CLEVELAND CLINIC LERNER COM-CWRU · PI DRAZBA, JUDY · 2010 to 2010
$500k
Specific-size hyaluronan in ALDR21AA024387 · NIAAA · CLEVELAND CLINIC LERNER COM-CWRU · PI NAGY, LAURA E. · 2016 to 2017
$416k
The Intestinal Role of Heme Oxygenase-1 in Alcoholic Liver DiseaseF31AA024017 · NIAAA · CLEVELAND CLINIC LERNER COM-CWRU · PI BELLOS, DAMIEN · 2015 to 2017
$101k
Roles and Regulation of Kupffer Cell Programmed Cell Death in Alcoholic Liver Disease PathogenesisF30AA026167 · NIAAA · CLEVELAND CLINIC LERNER COM-CWRU · PI WAT, JEANETTE J · 2017 to 2018
$78k
NCATS NIH HHS UL1 TR002548NCRR NIH HHS S10 RR026820NCRR NIH HHS UL1 RR024989NHLBI NIH HHS P01 HL107147NIAAA NIH HHS F30 AA026167NIAAA NIH HHS F31 AA024017NIAAA NIH HHS P50 AA024333NIAAA NIH HHS R01 AA026764NIAAA NIH HHS R21 AA024387
6 · The paper itself

Abstract

backgroundSpecific-sized species of the carbohydrate hyaluronan elicit a variety of cellular responses mediating tissue integrity and repair, as well as regulating inflammatory responses. Orally provided hyaluronan with an average molecular weight of 35 kDa (HA35) protects mice from short-term ethanol (EtOH)-induced liver injury. This protection was associated with maintenance of the colocalization of zonula occludens-1 (ZO-1) and occludin at tight junctions in the proximal colon. However, it is not known whether HA35 also protects other regions of the intestine or whether protection is due to a direct and/or indirect interaction of HA35 with the intestinal epithelium.

methodsFemale C57BL/6J mice were fed an EtOH containing diet or pair-fed control diet (4 days) and treated with or without HA35 via daily gavage during the last 3 days of EtOH feeding. Intestinal morphology and tight junction integrity were assessed. Differentiated Caco-2 cells were transfected or not with scrambled siRNA or siRNA targeting layilin, a hyaluronan receptor. Caco-2 cells were treated with or without HA35 prior to challenge with EtOH. Localization of tight junction proteins, fluorescein isothiocyanate (FITC)-dextran permeability, and transepithelial electrical resistance (TEER) were evaluated.

resultsWhile short-term EtOH did not result in any apparent changes in the gross morphology of the intestine, colocalization of ZO-1 and occludin at tight junctions was decreased in the proximal and distal colon. HA35 prevented these effects of EtOH. In differentiated Caco-2 cells, EtOH decreased the localization of ZO-1 and occludin at tight junctions and increased permeability of FITC-dextran. At higher concentrations, EtOH also decreased TEER. Pretreatment with HA35 prevented these changes. When the hyaluronan receptor layilin was knocked down in Caco-2 cells, HA35 no longer protected cells from EtOH-induced loss of tight junctions.

conclusionsTaken together, these data indicate that HA35 interacts with layilin on intestinal epithelial cells and maintains intestinal tight junction integrity during short-term EtOH exposure.

Indexed as

AnimalsCaco-2 CellsCentral Nervous System DepressantsDrug Evaluation, PreclinicalEpithelial CellsEthanolFemaleHumansHyaluronic AcidIntestinal MucosaLectins, C-TypeLiver Diseases, AlcoholicMice, Inbred C57BLTight JunctionsViscosupplementsCentral Nervous System DepressantsEthanolHyaluronic AcidLAYN protein, humanLectins, C-TypeViscosupplementsAlcoholic Liver DiseaseCaco-2Hyaluronic AcidIntestinal Epithelial CellsTight Junctions

Identifiers

PMID31237689
PMCPMC6721967
OpenAlexW2955846697

What OpenQuestion holds

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Registered trials

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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.