Evidence map›Paper›PMID 30284340›Full record

ArticleNeurogastroenterology and motility2019

Chronic stress and intestinal permeability: Lubiprostone regulates glucocorticoid receptor-mediated changes in colon epithelial tight junction proteins, barrier function, and visceral pain in the rodent and human.

Ye Zong, Shengtao Zhu, Shutian Zhang, Gen Zheng, John W Wiley, Shuangsong Hong

Open access · bronzeAbstract read
In one paragraph

Article in Neurogastroenterology and motility, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed, 1 pooled it
2.3field-weighted citation impact, top 11% 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

40 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.

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  10. Gut Microbiota-Driven Pathways Linking Chronic Stress to Tumor Progression.International journal of biological sciences · 2026
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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 at 2 institutions in 2 countries.

Ye ZongDepartment of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
Shengtao ZhuDepartment of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
Shutian ZhangDepartment of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
Gen ZhengDepartment of Internal Medicine, University of Michigan, Ann Arbor, Michigan.
John W WileyDepartment of Internal Medicine, University of Michigan, Ann Arbor, Michigan.
Shuangsong HongDepartment of Internal Medicine, University of Michigan, Ann Arbor, Michigan.ORCID 0000-0003-2488-8764
Capital Medical University · CNUniversity of Michigan · US

Funding

University of Michigan Center for Gastrointestinal ResearchP30DK034933 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI OWYANG, CHUNG · 1986 to 2021
$22.5M
Chronic Stress and Abdominal Pain: Novel MechanismsR01DK098205 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI WILEY, JOHN W · 2013 to 2017
$1.7M
Chronic Stress and Visceral Pain: Role of Intestinal Barrier DysfunctionR21AT009253 · NCCIH · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI HONG, SHUANGSONG, WILEY, JOHN W · 2016 to 2017
$527k
Chronic Stress and Visceral Pain Heterogeneity: Role of Endocannabinoid & Epigenetic Regulatory PathwaysR21NS113127 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI HONG, SHUANGSONG, WILEY, JOHN W · 2019 to 2020
$429k
National Center for Complementary and Alternative Medicine AT009253NCCIH NIH HHS R21 AT009253NIDDK NIH HHS DK098205NIDDK NIH HHS DK34933NIDDK NIH HHS P30 DK034933NIDDK NIH HHS R01 DK098205NINDS NIH HHS R21 NS113127University of Michigan P30 DK34933
6 · The paper itself

Abstract

backgroundChronic psychological stress is associated with increased intestinal epithelial permeability and visceral hyperalgesia. Lubiprostone, an agonist for chloride channel-2, promotes secretion and accelerates restoration of injury-induced epithelial barrier dysfunction. The mechanisms underlying how lubiprostone regulates colon epithelial barrier function and visceral hyperalgesia in chronic stress remain unknown.

methodsMale rats were subjected to water avoidance stress for 10 consecutive days. Lubiprostone was administered daily during the stress phase. Visceromotor response to colorectal distension was measured. Human colon crypts and cell lines were treated with cortisol and lubiprostone. The transepithelial electrical resistance and FITC-dextran permeability were assayed. Chromatin immunoprecipitation was conducted to assess glucocorticoid receptor binding at tight junction gene promoters. KEY

resultsLubiprostone significantly decreased chronic stress-induced visceral hyperalgesia in the rat (P < 0.05; n = 6). WA stress decreased occludin and claudin-1 and increased claudin-2 in rat colon crypts, which was prevented by lubiprostone. Cortisol treatment induced similar alterations of tight junction protein expression in Caco-2/BBE cells (P < 0.05) and significantly changed paracellular permeability in monolayers (P < 0.01). These changes were blocked by lubiprostone. Glucocorticoid receptor and its binding at occludin promoter region were decreased in cortisol-treated cells and human colon crypts, which was largely reversed by lubiprostone. In rat colonic cells, glucocorticoid receptor and its co-chaperone proteins were down-regulated after corticosterone treatment and lubiprostone reversed these changes. CONCLUSIONS & INFERENCES: Lubiprostone preferentially prevents chronic stress-induced alterations of intestinal epithelial tight junctions, barrier function, and visceral hyperalgesia that was associated with modulation of glucocorticoid receptor expression and function.

Indexed as

Stress, PsychologicalAnimalsCaco-2 CellsCell LineChloride Channel AgonistsCLC-2 Chloride ChannelsColonHumansIntestinal MucosaLubiprostoneMalePermeabilityRatsReceptors, GlucocorticoidTight Junction ProteinsVisceral PainChloride Channel AgonistsCLC-2 Chloride ChannelsClcn2 protein, ratLubiprostoneReceptors, GlucocorticoidTight Junction Proteinschronic stress; visceral hyperalgesiaglucocorticoid receptorintestinal permeabilitylubiprostonetight junction

Identifiers

PMID30284340
PMCPMC6347514
OpenAlexW2895688979

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.