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

Zundler S, Caioni M, Mueller M, Strauch U, Kunst C, Woelfel G (2016)

Publication Type: Journal article

Publication year: 2016

Journal

PLoS ONE Public Library of Science

Book Volume: 11

Pages Range: e0147736

Journal Issue: 1

DOI: 10.1371/journal.pone.0147736

Abstract

Potassium 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.In 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-? (IFN-?)-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).Inhibition 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-? 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.Taken together, we demonstrate that inhibition of KCNN4 differentially regulates IEC migration in IFN-?-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.

Authors with CRIS profile

Sebastian Zundler Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology

Involved external institutions

Universität Regensburg DE Germany (DE)

How to cite

APA:

Zundler, S., Caioni, M., Mueller, M., Strauch, U., Kunst, C., & Woelfel, G. (2016). K+ Channel Inhibition Differentially Regulates Migration of Intestinal Epithelial Cells in Inflamed vs. Non-Inflamed Conditions in a PI3K/Akt-Mediated Manner. PLoS ONE, 11(1), e0147736. https://doi.org/10.1371/journal.pone.0147736

MLA:

Zundler, Sebastian, et al. "K+ Channel Inhibition Differentially Regulates Migration of Intestinal Epithelial Cells in Inflamed vs. Non-Inflamed Conditions in a PI3K/Akt-Mediated Manner." PLoS ONE 11.1 (2016): e0147736.

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