Evidence map›Paper›PMID 32561494›Full record

ArticleCellular and molecular gastroenterology and hepatology2020

Decreased Colonic Activin Receptor-Like Kinase 1 Disrupts Epithelial Barrier Integrity in Patients With Crohn's Disease.

Takahiko Toyonaga, Erin C Steinbach, Benjamin P Keith, Jasmine B Barrow, Matthew R Schaner, Elisabeth A Wolber, Caroline Beasley, Jennifer Huling, Yuli Wang, Nancy L Allbritton and 14 more

Open access · goldAbstract read
In one paragraph

Article in Cellular and molecular gastroenterology and hepatology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
0.8field-weighted citation impact, top 26% 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

12 citing papers in PubMed, 22 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

24 authors at 3 institutions in 1 country.

Takahiko ToyonagaCenter for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Erin C SteinbachCenter for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Division of Rheumatology, Allergy and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Benjamin P KeithCenter for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Department of Genetics, Department of Biology, Curriculum in Bioinformatics and Computational Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Jasmine B BarrowCenter for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Matthew R SchanerCenter for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Elisabeth A WolberCenter for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Caroline BeasleyCenter for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Jennifer HulingJoint Department of Biomedical Engineering, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Yuli WangJoint Department of Biomedical Engineering, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Nancy L AllbrittonJoint Department of Biomedical Engineering, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Nicole ChaumontDepartment of Surgery, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Timothy S SadiqDepartment of Surgery, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Mark J KorudaDepartment of Surgery, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Animesh JainCenter for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Millie D LongCenter for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Edward L BarnesCenter for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Hans H HerfarthCenter for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Kim L IsaacsCenter for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Jonathan J HansenCenter for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Michael T ShanahanDepartment of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York.
Reza RahbarDepartment of Surgery, Rex Healthcare of Wakefield, North Carolina.
Terrence S FureyCenter for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Department of Genetics, Department of Biology, Curriculum in Bioinformatics and Computational Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Praveen SethupathyDepartment of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York.
Shehzad Z SheikhCenter for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. Electronic address: shehzad_sheikh@med.unc.edu.
University of North Carolina at Chapel Hill · USCornell University · USRex Hospital · US

Funding

Virology Research Program (Program 4)P30CA016086 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Deborah F. Tate · 1985 to 2026
$201.5M
PILOT AND FEASIBILITY STUDIESP30DK034987 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI ROBERT S. SANDLER · 1985 to 2026
$30.5M
Role of IL-10 in APC Regulation of Protective vs. Pathogenic T Cell Responses toP01DK094779 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SHEIKH, SHEHZAD Z. · 2013 to 2023
$17.9M
GASTROENTEROLOGY RESEARCH TRAININGT32DK007737 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SHEHZAD Z. SHEIKH · 1996 to 2026
$7.8M
DEVELOPMENT OF HUMAN INTESTINAL SIMULACRAR01DK109559 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI ALLBRITTON, NANCY L., BULTMAN, SCOTT J · 2015 to 2019
$5.2M
Development of a microphysiologic system to assay the interaction of the human colonic epithelium on Clostridium difficileR01DK120606 · NIDDK · UNIVERSITY OF WASHINGTON · PI ALLBRITTON, NANCY L., SHEIKH, SHEHZAD Z. · 2020 to 2023
$2.2M
Integrative Genetic and Genomic Analyses in the Inflammatory Bowel DiseaseR01DK104828 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI FUREY, TERRENCE S., SHEIKH, SHEHZAD Z. · 2016 to 2018
$901k
NCI NIH HHS P30 CA016086NIAID NIH HHS L40 AI147229NIDDK NIH HHS P01 DK094779NIDDK NIH HHS P30 DK034987NIDDK NIH HHS R01 DK104828NIDDK NIH HHS R01 DK109559NIDDK NIH HHS R01 DK120606NIDDK NIH HHS T32 DK007737
6 · The paper itself

Abstract

BACKGROUND &

aimsIntestinal epithelial cell (IEC) barrier dysfunction is critical to the development of Crohn's disease (CD). However, the mechanism is understudied. We recently reported increased microRNA-31-5p (miR-31-5p) expression in colonic IECs of CD patients, but downstream targets and functional consequences are unknown.

methodsmicroRNA-31-5p target genes were identified by integrative analysis of RNA- and small RNA-sequencing data from colonic mucosa and confirmed by quantitative polymerase chain reaction in colonic IECs. Functional characterization of activin receptor-like kinase 1 (ACVRL1 or ALK1) in IECs was performed ex vivo using 2-dimensional cultured human primary colonic IECs. The impact of altered colonic ALK1 signaling in CD for the risk of surgery and endoscopic relapse was evaluated by a multivariate regression analysis and a Kaplan-Meier estimator.

resultsALK1 was identified as a target of miR-31-5p in colonic IECs of CD patients and confirmed using a 3'-untranslated region reporter assay. Activation of ALK1 restricted the proliferation of colonic IECs in a 5-ethynyl-2-deoxyuridine proliferation assay and down-regulated the expression of stemness-related genes. Activated ALK1 signaling increased colonic IEC differentiation toward colonocytes. Down-regulated ALK1 signaling was associated with increased stemness and decreased colonocyte-specific marker expression in colonic IECs of CD patients compared with healthy controls. Activation of ALK1 enhanced epithelial barrier integrity in a transepithelial electrical resistance permeability assay. Lower colonic ALK1 expression was identified as an independent risk factor for surgery and was associated with a higher risk of endoscopic relapse in CD patients.

conclusionsDecreased colonic ALK1 disrupted colonic IEC barrier integrity and was associated with poor clinical outcomes in CD patients.

Indexed as

Activin Receptors, Type IIAdultColonCrohn DiseaseDown-RegulationEnzyme ActivationFemaleHumansIntestinal MucosaMaleMicroRNAsMiddle AgedActivin Receptors, Type IIACVRL1 protein, humanMicroRNAsMIRN31 microRNA, humanALK1Inflammatory Bowel DiseaseIntestinal Epithelial BarriermiR-31

Identifiers

PMID32561494
PMCPMC7502566
OpenAlexW3036815077

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.