Evidence map›Paper›PMID 33617890›Full record

ArticleGastroenterology2021

The Colonic Mucosal MicroRNAs, MicroRNA-219a-5p, and MicroRNA-338-3p Are Downregulated in Irritable Bowel Syndrome and Are Associated With Barrier Function and MAPK Signaling.

Swapna Mahurkar-Joshi, Carl Robert Rankin, Elizabeth Jane Videlock, Artin Soroosh, Abhishek Verma, Ariela Khandadash, Dimitrios Iliopoulos, Charalabos Pothoulakis, Emeran A Mayer, Lin Chang

Open access · greenAbstract read
In one paragraph

Article in Gastroenterology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed, 1 pooled it
3.3field-weighted citation impact, top 7% 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

34 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.

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  9. The road to Rome IV and beyond: Evolution, refinements and future considerations for the Rome criteria for functional gastrointestinal disorders.Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology · 2025
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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

10 authors at 1 institution in 1 country.

Swapna Mahurkar-JoshiG. Oppenheimer Center for Neurobiology of Stress and Resilience, Division of Digestive Diseases, Department of Medicine, University of California, Los Angeles, Los Angeles, California.
Carl Robert RankinUCLA Center for Inflammatory Bowel Diseases, Division of Digestive Diseases, Department of Medicine, University of California, Los Angeles, Los Angeles, California.
Elizabeth Jane VidelockG. Oppenheimer Center for Neurobiology of Stress and Resilience, Division of Digestive Diseases, Department of Medicine, University of California, Los Angeles, Los Angeles, California.
Artin SorooshUCLA Center for Inflammatory Bowel Diseases, Division of Digestive Diseases, Department of Medicine, University of California, Los Angeles, Los Angeles, California.
Abhishek VermaG. Oppenheimer Center for Neurobiology of Stress and Resilience, Division of Digestive Diseases, Department of Medicine, University of California, Los Angeles, Los Angeles, California.
Ariela KhandadashG. Oppenheimer Center for Neurobiology of Stress and Resilience, Division of Digestive Diseases, Department of Medicine, University of California, Los Angeles, Los Angeles, California.
Dimitrios IliopoulosUCLA Center for Inflammatory Bowel Diseases, Division of Digestive Diseases, Department of Medicine, University of California, Los Angeles, Los Angeles, California.
Charalabos PothoulakisUCLA Center for Inflammatory Bowel Diseases, Division of Digestive Diseases, Department of Medicine, University of California, Los Angeles, Los Angeles, California.
Emeran A MayerG. Oppenheimer Center for Neurobiology of Stress and Resilience, Division of Digestive Diseases, Department of Medicine, University of California, Los Angeles, Los Angeles, California.
Lin ChangG. Oppenheimer Center for Neurobiology of Stress and Resilience, Division of Digestive Diseases, Department of Medicine, University of California, Los Angeles, Los Angeles, California. Electronic address: linchang@mednet.ucla.edu.
University of California, Los Angeles · US

Funding

UCLA Clinical Translational Science InstituteUL1TR001881 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARLEEN F. BROWN, ARASH NAEIM · 2016 to 2026
$118.1M
UCLA Clinical and Translational Science InstituteUL1TR000124 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2012 to 2015
$57.0M
Pilot and Feasibility ProgramP30DK041301 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ROZENGURT, JUAN ENRIQUE · 1990 to 2019
$18.0M
Women's Health and Functional Visceral Disorders CenterP50DK064539 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI MAYER, EMERAN A · 2002 to 2017
$17.5M
DNA Methylation Based Biomarkers and Epigenetic Regulation in IBSR21DK104078 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI CHANG, LIN · 2015 to 2016
$424k
NCATS NIH HHS UL1 TR000124NCATS NIH HHS UL1 TR001881NIDDK NIH HHS P30 DK041301NIDDK NIH HHS P50 DK064539NIDDK NIH HHS R21 DK104078
6 · The paper itself

Abstract

BACKGROUND &

aimsAlterations in microRNA (miRNA) and in the intestinal barrier are putative risk factors for irritable bowel syndrome (IBS). We aimed to identify differentially expressed colonic mucosal miRNAs, their targets in IBS compared to healthy controls (HCs), and putative downstream pathways.

methodsTwenty-nine IBS patients (15 IBS with constipation [IBS-C], 14 IBS with diarrhea [IBS-D]), and 15 age-matched HCs underwent sigmoidoscopy with biopsies. A nCounter array was used to assess biopsy specimen-associated miRNA levels. A false discovery rate (FDR) < 10% was considered significant. Real-time polymerase chain reaction (PCR) was used to validate differentially expressed genes. To assess barrier function, trans-epithelial electrical resistance (TEER) and dextran flux assays were performed on Caco-2 intestinal epithelial cells that were transfected with miRNA-inhibitors or control inhibitors. Protein expression of barrier function associated genes was confirmed using western blots.

resultsFour out of 247 miRNAs tested were differentially expressed in IBS compared to HCs (FDR < 10%). Real-time PCR validation suggested decreased levels of miR-219a-5p and miR-338-3p in IBS (P = .026 and P = .004), and IBS-C (P = .02 and P = .06) vs. HCs as the strongest associations. Inhibition of miR-219a-5p resulted in altered expression of proteasome/barrier function genes. Functionally, miR-219a-5p inhibition enhanced the permeability of intestinal epithelial cells as TEER was reduced (25-50%, P < .05) and dextran flux was increased (P < .01). Additionally, inhibition of miR-338-3p in cells caused alterations in the mitogen-activated protein kinase (MAPK) signaling pathway genes.

conclusionTwo microRNAs that potentially affect permeability and visceral nociception were identified to be altered in IBS patients. MiR-219a-5p and miR-338-3p potentially alter barrier function and visceral hypersensitivity via neuronal and MAPK signaling and could be therapeutic targets in IBS.

Indexed as

AdolescentAdultCase-Control StudiesColonConstipationDiarrheaDown-RegulationFemaleHumansIntestinal MucosaIrritable Bowel SyndromeMaleMAP Kinase Signaling SystemMicroRNAsMiddle AgedPermeabilityMicroRNAsMIRN219 microRNA, humanMIRN338 microRNA, humanBarrier FunctionMAPK SignalingmiR-219a-5pmiR-338-3pmiRNA

Identifiers

PMID33617890
PMCPMC8169529
OpenAlexW3129354815

What Socratic 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 Socratic graph.