Evidence map›Paper›PMID 22271547›Full record

ArticleInflammatory bowel diseases2012

AMP-18 facilitates assembly and stabilization of tight junctions to protect the colonic mucosal barrier.

Peili Chen, Sreedharan Kartha, Marc Bissonnette, John Hart, F Gary Toback

Open access · bronzeAbstract read
In one paragraph

Article in Inflammatory bowel diseases, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.6field-weighted citation impact, top 18% 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

13 citing papers in PubMed, 20 citations in OpenAlex.

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  7. Sex- and corticotropin-releasing factor receptor 2- dependent actions of urocortin 1 during inflammation.American journal of physiology. Regulatory, integrative and comparative physiology · 2016
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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

5 authors at 1 institution in 1 country.

Peili ChenDepartment of Medicine, University of Chicago, Chicago, Illinois 60637, USA.
Sreedharan Kartha
Marc Bissonnette
John Hart
F Gary Toback
University of Chicago · US

Funding

ULTRASTRUCTURE AND CYTOMORPHOLOGY COREP30DK042086 · NIDDK · UNIVERSITY OF CHICAGO · PI LIU, CAMBRIAN YANGSHAO · 1990 to 2025
$29.8M
Roles of ErbB Signaling in Colonic CarcinogenesisR01CA036745 · NCI · UNIVERSITY OF CHICAGO · PI BISSONNETTE, BRUCE MARC · 1985 to 2007
$2.3M
Targeting Tight Junctions To Treat MucositisR21DE018811 · NIDCR · UNIVERSITY OF CHICAGO · PI TOBACK, FREDERICK GARY · 2009 to 2010
$429k
COLONIC EPITHELIAL CELL PLASMA MEMBRANESR37CA036745 · NCI · UNIVERSITY OF CHICAGO · PI BRASITUS, THOMAS A · 1986 to 1999
–
NCI NIH HHS CA036745NCI NIH HHS R01 CA036745NCI NIH HHS R37 CA036745NIDCR NIH HHS R21 DE018811NIDDK NIH HHS P30 DK042086NIDDK NIH HHS P30DK42086
6 · The paper itself

Abstract

backgroundInflammatory bowel disease (IBD) is characterized by an injured epithelium. Development of agents that could enhance mucosal healing is a major goal in IBD therapeutics. The 18-kDa antrum mucosal protein (AMP-18) and a 21-mer peptide derived from AMP-18 stimulate accumulation of tight junction (TJ) proteins in cultured epithelial cells and mouse colonic mucosa to protect the mucosal barrier, suggesting it might be a useful agent to treat IBD.

methodsWe searched for molecular mechanisms by which AMP peptide or recombinant AMP-18 act on TJs in intact cell monolayers, or those disrupted by low-calcium medium. Roles of the p38 mitogen-activated protein kinase (MAPK) / heat shock protein (hsp)25 pathway and PKCζ were investigated by immunoblotting and confocal microscopy.

resultsAMP peptide activated p38 MAPK, which subsequently phosphorylated hsp25. Accumulated phospho-hsp25 was associated with perijunctional actin. AMP-18 also induced rapid phosphorylation of PKCζ and its colocalization with perijunctional actin in Caco2/bbe cells, which was accompanied by translocation and formation of complexes of "polarity proteins" in the TJ-containing detergent-insoluble fraction. Treatment with AMP-18 also stimulated accumulation of ZO-1, ZO-2, and JAM-A in nascent TJs known to associate with the multimeric p-PKCζ/Par6/ Cdc42/ECT2·GTP/Par3 polarity protein complex.

conclusionsAMP-18 facilitates translocation and assembly of multiple proteins into TJs and their association with and subsequent stabilization of the actin filament network. We speculate that improved barrier function induced by AMP-18 is mediated by enhanced TJ assembly. Thus, AMP-18 may provide a promising lead to develop agents effective in healing injured colonic epithelium in IBD.

Indexed as

AnimalsCaco-2 CellsCalciumCells, CulturedColitisColonDextran SulfateFluorescent Antibody Technique, IndirectHeat-Shock ProteinsHSP27 Heat-Shock ProteinsHumansIntestinal MucosaMaleMiceMice, Inbred C57BLMolecular ChaperonesCalciumDextran SulfateGKN1 protein, humanHeat-Shock ProteinsHSP27 Heat-Shock ProteinsHSPB1 protein, humanMolecular Chaperonesp38 Mitogen-Activated Protein KinasesPeptide FragmentsPeptide HormonesProtein Kinase CProtein Kinase C zeta

Identifiers

PMID22271547
PMCPMC3337967
OpenAlexW1975405454

What OpenQuestion holds

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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.