Evidence map›Paper›PMID 24665409›Full record

ArticleTissue barriers2013

Novel mechanism of cytokine-induced disruption of epithelial barriers: Janus kinase and protein kinase D-dependent downregulation of junction protein expression.

Nayden G Naydenov, Somesh Baranwal, Shadab Khan, Alex Feygin, Pooja Gupta, Andrei I Ivanov

Open access · hybridAbstract read
In one paragraph

Article in Tissue barriers, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
3.5field-weighted citation impact, top 8% 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

24 citing papers in PubMed, 31 citations in OpenAlex.

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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 3 institutions in 2 countries.

Nayden G NaydenovDepartment of Human and Molecular Genetics, Virginia Commonwealth University School of Medicine, Richmond, VA USA;
Somesh BaranwalDepartment of Human and Molecular Genetics, Virginia Commonwealth University School of Medicine, Richmond, VA USA;
Shadab KhanDepartment of Medicine, University of Rochester School of Medicine, Rochester, NY USA.
Alex FeyginDepartment of Human and Molecular Genetics, Virginia Commonwealth University School of Medicine, Richmond, VA USA;
Pooja GuptaDepartment of Human and Molecular Genetics, Virginia Commonwealth University School of Medicine, Richmond, VA USA;
Andrei I IvanovDepartment of Human and Molecular Genetics, Virginia Commonwealth University School of Medicine, Richmond, VA USA; ; VCU Institute of Molecular Medicine; Virginia Commonwealth University School of Medicine; Richmond, VA USA ; VCU Massey Cancer Center; Virginia Commonwealth University School of Medicine; Richmond, VA USA.
Virginia Commonwealth University · USUniversity of Richmond · USUniversity of Rochester · US

Funding

Junctional exocytosis and breakdown of the intestinal barrier in inflammationR01DK083968 · NIDDK · VIRGINIA COMMONWEALTH UNIVERSITY · PI IVANOV, ANDREI IVANOVICH · 2010 to 2014
$1.6M
Actin dynamics and regulation of epithelial barrier in intestinal inflammationR01DK084953 · NIDDK · VIRGINIA COMMONWEALTH UNIVERSITY · PI IVANOV, ANDREI IVANOVICH · 2010 to 2013
$1.3M
NIDDK NIH HHS R01 DK083968NIDDK NIH HHS R01 DK084953
6 · The paper itself

Abstract

The ductal epithelium plays a key role in physiological secretion of pancreatic enzymes into the digestive system. Loss of barrier properties of the pancreatic duct may contribute to the development of pancreatitis and metastatic dissemination of pancreatic tumors. Proinflammatory cytokines are essential mediators of pancreatic inflammation and tumor progression; however, their effects on the integrity and barrier properties of the ductal epithelium have not been previously addressed. In the present study, we investigate mechanisms of cytokine-induced disassembly of tight junctions (TJs) and adherens junctions (AJs) in a model pancreatic epithelium. Exposure of HPAF-II human pancreatic epithelial cell monolayers to interferon (IFN)γ disrupted integrity and function of apical junctions as manifested by increased epithelial permeability and cytosolic translocation of AJ and TJ proteins. Tumor necrosis factor (TNF)α potentiated the effects of IFNγ on pancreatic epithelial junctions. The cytokine-induced increase in epithelial permeability and AJ/TJ disassembly was attenuated by pharmacological inhibition of Janus kinase (JAK) and protein kinase D (PKD). Loss of apical junctions in IFNγ/TNFα-treated HPAF-II cells was accompanied by JAK and PKD dependent decrease in expression of AJ (E-cadherin, p120 catenin) and TJ (occludin, ZO-1) proteins. Depletion of E-cadherin or p120 catenin recapitulated the effects of cytokines on HPAF-II cell permeability and junctions. Our data suggests that proinflammatory cytokines disrupt pancreatic epithelial barrier via expressional downregulation of key structural components of AJs and TJs. This mechanism is likely to be important for pancreatic inflammatory injury and tumorigenesis.

Indexed as

adherens junctionsinterferonpancreatitistight junctionstumor necrosis factor

Identifiers

PMID24665409
PMCPMC3783224
OpenAlexW1995640884

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.