Evidence map›Paper›PMID 32516134›Full record

ArticleThe Journal of clinical investigation2020

Inactivation of paracellular cation-selective claudin-2 channels attenuates immune-mediated experimental colitis in mice.

Preeti Raju, Nitesh Shashikanth, Pei-Yun Tsai, Pawin Pongkorpsakol, Sandra Chanez-Paredes, Peter R Steinhagen, Wei-Ting Kuo, Gurminder Singh, Sachiko Tsukita, Jerrold R Turner

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.

0numbers the graph read from it
0cells of the map it votes in
88citing papers in PubMed
6.5field-weighted citation impact, top 3% 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

88 citing papers in PubMed, 119 citations in OpenAlex.

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  5. Temporal transcriptomic profiling identifies core regulators in cytokine-induced gut barrier disruption in differentiated Caco-2 cells.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026
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  10. Tight Junction Defects in Aganglionic and Ganglionic Colon in Children With Hirschsprung Disease.Laboratory investigation; a journal of technical methods and pathology · 2026
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28 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 2 countries.

Preeti RajuLaboratory of Mucosal Barrier Pathobiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Nitesh ShashikanthLaboratory of Mucosal Barrier Pathobiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Pei-Yun TsaiDepartment of Pathology, University of Chicago, Chicago, Illinois, USA.
Pawin PongkorpsakolLaboratory of Mucosal Barrier Pathobiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Sandra Chanez-ParedesLaboratory of Mucosal Barrier Pathobiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Peter R SteinhagenLaboratory of Mucosal Barrier Pathobiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Wei-Ting KuoLaboratory of Mucosal Barrier Pathobiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Gurminder SinghLaboratory of Mucosal Barrier Pathobiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Sachiko TsukitaLaboratory of Biological Science, Graduate School of Frontier Biosciences and Graduate School of Medicine, Osaka University, Osaka, Japan.
Jerrold R TurnerLaboratory of Mucosal Barrier Pathobiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Brigham and Women's Hospital · USThe University of Osaka · JPUniversity of Chicago · US

Funding

STRUCTURE-FUNCTION RELATIONSHIPS IN THE ALIMENTARY TRACTP30DK034854 · NIDDK · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI JONATHAN C KAGAN · 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
NIDDK NIH HHS P30 DK034854NIDDK NIH HHS R01 DK061931NIDDK NIH HHS R01 DK068271NIDDK NIH HHS R24 DK099803
6 · The paper itself

Abstract

The tight junction protein claudin-2 is upregulated in disease. Although many studies have linked intestinal barrier loss to local and systemic disease, these have relied on macromolecular probes. In vitro analyses show, however, that these probes cannot be accommodated by size- and charge-selective claudin-2 channels. We sought to define the impact of claudin-2 channels on disease. Transgenic claudin-2 overexpression or IL-13-induced claudin-2 upregulation increased intestinal small cation permeability in vivo. IL-13 did not, however, affect permeability in claudin-2-knockout mice. Claudin-2 is therefore necessary and sufficient to effect size- and charge-selective permeability increases in vivo. In chronic disease, T cell transfer colitis severity was augmented or diminished in claudin-2-transgenic or -knockout mice, respectively. We translated the in vitro observation that casein kinase-2 (CK2) inhibition blocks claudin-2 channel function to prevent acute, IL-13-induced, claudin-2-mediated permeability increases in vivo. In chronic immune-mediated colitis, CK2 inhibition attenuated progression in claudin-2-sufficient, but not claudin-2-knockout, mice, i.e., the effect was claudin-2 dependent. Paracellular flux mediated by claudin-2 channels can therefore promote immune-mediated colitis progression. Although the mechanisms by which claudin-2 channels intensify disease remain to be defined, these data suggest that claudin-2 may be an accessible target in immune-mediated disorders, including inflammatory bowel disease.

Indexed as

AnimalsClaudinsColitisDisease Models, AnimalFemaleHumansInterleukin-13Intestinal MucosaMaleMiceMice, Inbred C57BLMice, KnockoutMice, TransgenicUp-RegulationClaudinsCLDN2 protein, humanCldn2 protein, mouseInterleukin-13Cell BiologyEpithelial transport of ions and waterGastroenterologyInflammatory bowel diseaseTight junctions

Identifiers

PMID32516134
PMCPMC7524482
OpenAlexW3032914467

What OpenQuestion holds

Textmetadata
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.