Evidence map›Paper›PMID 31401143›Full record

ArticleGastroenterology2019

Inflammation-induced Occludin Downregulation Limits Epithelial Apoptosis by Suppressing Caspase-3 Expression.

Wei-Ting Kuo, Le Shen, Li Zuo, Nitesh Shashikanth, Ma Lora Drizella M Ong, Licheng Wu, Juanmin Zha, Karen L Edelblum, Yitang Wang, Yingmin Wang and 2 more

Open access · greenAbstract read
In one paragraph

Article in Gastroenterology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 149 papers.

0numbers the graph read from it
0cells of the map it votes in
149citing papers in PubMed
8.5field-weighted citation impact, top 2% 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

149 citing papers in PubMed, 244 citations in OpenAlex.

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  16. Tight Junction Defects in Aganglionic and Ganglionic Colon in Children With Hirschsprung Disease.Laboratory investigation; a journal of technical methods and pathology · 2026
    Article
  17. Article
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  19. Review
  20. Review

89 more citing papers are in PubMed but not listed here.

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

12 authors at 4 institutions in 2 countries.

Wei-Ting KuoLaboratory of Mucosal Barrier Pathobiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
Le ShenDepartment of Pathology, The University of Chicago, Chicago, Illinois.
Li ZuoLaboratory of Mucosal Barrier Pathobiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Anhui Medical University, Hefei, Anhui, China.
Nitesh ShashikanthLaboratory of Mucosal Barrier Pathobiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
Ma Lora Drizella M OngLaboratory of Mucosal Barrier Pathobiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
Licheng WuDepartment of Pathology, The University of Chicago, Chicago, Illinois.
Juanmin ZhaDepartment of Pathology, The University of Chicago, Chicago, Illinois; Soochow University and Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, China.
Karen L EdelblumDepartment of Pathology, The University of Chicago, Chicago, Illinois; Department of Pathology and Laboratory Medicine, Center for Inflammation and Immunity, Rutgers New Jersey Medical School, Newark, New Jersey.
Yitang WangDepartment of Pathology, The University of Chicago, Chicago, Illinois.
Yingmin WangDepartment of Pathology, The University of Chicago, Chicago, Illinois.
Steven P NilsenLaboratory of Mucosal Barrier Pathobiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
Jerrold R TurnerLaboratory of Mucosal Barrier Pathobiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Department of Pathology, The University of Chicago, Chicago, Illinois. Electronic address: jrturner@bwh.harvard.edu.
Brigham and Women's Hospital · USUniversity of Chicago · USRutgers, The State University of New Jersey · USSoochow University · CN

Funding

STRUCTURE-FUNCTION RELATIONSHIPS IN THE ALIMENTARY TRACTP30DK034854 · NIDDK · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI LYNN BRY · 1986 to 2026
$32.4M
ZO-1-MEDIATED PROTEIN INTERACTIONS: REGULATORS AND INTEGRATORS OF DIVERSE EPITHELIAL FUNCTIONS IN HEALTH AND DISEASER01DK061931 · NIDDK · UNIVERSITY OF CHICAGO · PI JERROLD R. TURNER · 2001 to 2026
$15.0M
Therapeutic targeting of protein interactions to reverse MLCK1-mediated intestinal barrier loss and ameliorate disease.R01DK068271 · NIDDK · UNIVERSITY OF CHICAGO · PI JERROLD R. TURNER · 2005 to 2026
$11.3M
Translational Approaches to Develop Drug Therapy for DiarrheaR24DK099803 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI DONOWITZ, MARK · 2014 to 2019
$8.9M
Contribution of occludin to intestinal homeostasis and diseaseK01DK092381 · NIDDK · UNIVERSITY OF CHICAGO · PI SHEN, LE · 2012 to 2016
$751k
NIDDK NIH HHS K01 DK092381NIDDK NIH HHS P30 DK034854NIDDK NIH HHS R01 DK061931NIDDK NIH HHS R01 DK068271NIDDK NIH HHS R24 DK099803
6 · The paper itself

Abstract

BACKGROUND &

aimsEpithelial tight junctions are compromised in gastrointestinal disease. Processes that contribute to the resulting barrier loss include endocytic occludin removal from the tight junction and reduced occludin expression. Nevertheless, the relatively-normal basal phenotype of occludin knockout (KO) mice has been taken as evidence that occludin does not contribute to gastrointestinal barrier function. We asked whether stress could unmask occludin functions within intestinal epithelia.

methodsWildtype (WT), universal and intestinal epithelial-specific occludin KO, and villin-EGFP-occludin transgenic mice as well as WT and occludin knockdown (KD) Caco-2

resultsIntestinal epithelial occludin loss limited severity of DSS- and TNBS-induced colitis due to epithelial resistance to apoptosis; activation of both intrinsic and extrinsic apoptotic pathways was blocked in occludin KO epithelia. Promoter analysis revealed that occludin enhances CASP3 transcription and, conversely, that occludin downregulation reduces caspase-3 expression. Analysis of biopsies from Crohn's disease and ulcerative colitis patients and normal controls demonstrated that disease-associated occludin downregulation was accompanied by and correlated with reduced caspase-3 expression. In vitro, cytokine-induced occludin downregulation resulted in reduced caspase-3 expression and resistance to intrinsic and extrinsic pathway apoptosis, demonstrating an overall protective effect of inflammation-induced occludin loss.

conclusionsThe tight junction protein occludin regulates apoptosis by enhancing caspase-3 transcription. These data suggest that reduced epithelial caspase-3 expression downstream of occludin downregulation is a previously-unappreciated anti-apoptotic process that contributes to mucosal homeostasis in inflammatory conditions.

Indexed as

ApoptosisAnimalsCaco-2 CellsCase-Control StudiesCaspase 3ColitisColitis, UlcerativeColonCrohn DiseaseDextran SulfateDisease Models, AnimalEpithelial CellsHumansIntestinal MucosaMice, Inbred C57BLMice, KnockoutCASP3 protein, humanCasp3 protein, mouseCaspase 3Dextran SulfateOccludinOCLN protein, humanOcln protein, mouseTjp1 protein, mouseTrinitrobenzenesulfonic AcidZonula Occludens-1 ProteinCell DeathGene RegulationIBDPermeability

Identifiers

PMID31401143
PMCPMC6815722
OpenAlexW2967076383

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.