Evidence map›Paper›PMID 26824610›Full record

ArticlePloS one2016

K+ Channel Inhibition Differentially Regulates Migration of Intestinal Epithelial Cells in Inflamed vs. Non-Inflamed Conditions in a PI3K/Akt-Mediated Manner.

Sebastian Zundler, Massimiliano Caioni, Martina Müller, Ulrike Strauch, Claudia Kunst, Gisela Woelfel

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed, 1 pooled it
1.2field-weighted citation impact, top 20% 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

8 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Review
  5. Review
  6. Article
  7. Histone Deacetylases Enhance CaInternational journal of molecular sciences · 2018
    Article
  8. KPflugers Archiv : European journal of physiology · 2016
    Article
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 1 institution in 1 country.

Sebastian ZundlerDepartment of Internal Medicine I, Regensburg University Medical Center, Regensburg, Germany.
Massimiliano CaioniDepartment of Internal Medicine I, Regensburg University Medical Center, Regensburg, Germany.
Martina MüllerDepartment of Internal Medicine I, Regensburg University Medical Center, Regensburg, Germany.
Ulrike StrauchDepartment of Internal Medicine I, Regensburg University Medical Center, Regensburg, Germany.
Claudia KunstDepartment of Internal Medicine I, Regensburg University Medical Center, Regensburg, Germany.
Gisela WoelfelDepartment of Internal Medicine I, Regensburg University Medical Center, Regensburg, Germany.
Friedrich-Alexander-Universität Erlangen-Nürnberg · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPotassium channels have been shown to determine wound healing in different tissues, but their role in intestinal epithelial restitution--the rapid closure of superficial wounds by intestinal epithelial cells (IEC)--remains unclear.

methodsIn this study, the regulation of IEC migration by potassium channel modulation was explored with and without additional epidermal growth factor (EGF) under baseline and interferon-γ (IFN-γ)-pretreated conditions in scratch assays and Boyden chamber assays using the intestinal epithelial cell lines IEC-18 and HT-29. To identify possibly involved subcellular pathways, Western Blot (WB)-analysis of ERK and Akt phosphorylation was conducted and PI3K and ERK inhibitors were used in scratch assays. Furthermore, mRNA-levels of the potassium channel KCNN4 were determined in IEC from patients suffering from inflammatory bowel diseases (IBD).

resultsInhibition of Ca(2+)-dependent potassium channels significantly increased intestinal epithelial restitution, which could not be further promoted by additional EGF. In contrast, inhibition of KCNN4 after pretreatment with IFN-γ led to decreased or unaffected migration. This effect was abolished by EGF. Changes in Akt, but not in ERK phosphorylation strongly correlated with these findings and PI3K but not ERK inhibition abrogated the effect of KCNN4 inhibition. Levels of KCNN4 mRNA were higher in samples from IBD patients compared with controls.

conclusionsTaken together, we demonstrate that inhibition of KCNN4 differentially regulates IEC migration in IFN-γ-pretreated vs. non pretreated conditions. Moreover, our data propose that the PI3K signaling cascade is responsible for this differential regulation. Therefore, we present a cellular model that contributes new aspects to epithelial barrier dysfunction in chronic intestinal inflammation, resulting in propagation of inflammation and symptoms like ulcers or diarrhea.

Indexed as

AnimalsAnimals, NewbornBiological AssayCell LineCell MovementDiffusion Chambers, CultureEpidermal Growth FactorEpithelial CellsGene Expression RegulationHT29 CellsHumansIleumInflammatory Bowel DiseasesInterferon-gammaIntermediate-Conductance Calcium-Activated Potassium ChannelsMitogen-Activated Protein Kinase 1Epidermal Growth FactorInterferon-gammaIntermediate-Conductance Calcium-Activated Potassium ChannelsKCNN4 protein, humanKcnn4 protein, ratMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Phosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsProtein Kinase InhibitorsProto-Oncogene Proteins c-akt

Identifiers

PMID26824610
PMCPMC4732808
OpenAlexW2252681143

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.