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

PloS One
Sebastian ZundlerGisela Woelfel

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-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). 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-γ led to decreased or unaffected migration. This effect was abolished by EGF. Changes in Akt, but not in ERK phosphorylation strongly correlated with...Continue Reading

References

Jul 24, 1975·Nature·W F BenedictA E Freeman
Apr 17, 1997·Biochemical and Biophysical Research Communications·B K DieckgraefeD H Alpers
Jul 1, 1997·The Journal of Clinical Investigation·M F SantosG Tigyi
Jul 10, 1999·Pflügers Archiv : European journal of physiology·A SchwabP C Dartsch
Jan 29, 2000·Pflügers Archiv : European journal of physiology·S W SchneiderA Schwab
Feb 29, 2000·The Journal of General Physiology·Y Jiang, R MacKinnon
Mar 10, 2001·Inflammatory Bowel Diseases·A U Dignass
Feb 15, 2002·Pflügers Archiv : European journal of physiology·L J MacVinishA W Cuthbert
Feb 16, 2002·Methods : a Companion to Methods in Enzymology·K J Livak, T D Schmittgen
Feb 21, 2002·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Wenjiang ZhangEdward M Sellers
Oct 24, 2002·Current Opinion in Clinical Nutrition and Metabolic Care·Daniel C Baumgart, Axel U Dignass
Jun 27, 2003·American Journal of Physiology. Cell Physiology·Laurence J EganMartin F Kagnoff
Aug 2, 2003·Journal of Cell Science·Sylvain Merlot, Richard A Firtel
Sep 6, 2003·American Journal of Physiology. Gastrointestinal and Liver Physiology·Lone S BertelsenKim E Barrett
Oct 31, 2003·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Roger RezzonicoHeidy Schmid-Antomarchi
Sep 11, 2004·American Journal of Physiology. Gastrointestinal and Liver Physiology·Terence ChiuEnrique Rozengurt
Sep 25, 2004·Journal of Cellular Physiology·Srisaila BasavappaUma Sundaram
Sep 30, 2004·Wound Repair and Regeneration : Official Publication of the Wound Healing Society [and] the European Tissue Repair Society·Margaret M LotzJeffrey B Matthews
Dec 7, 2005·Proceedings of the National Academy of Sciences of the United States of America·Jan WehkampCharles L Bevins
Jun 10, 2006·American Journal of Physiology. Gastrointestinal and Liver Physiology·Hui DongJimmy Y Chow
Oct 13, 2006·Clinical and Experimental Immunology·R ItoO Mazda
Oct 27, 2006·Trends in Cell Biology·Annarosa Arcangeli, Andrea Becchetti
May 24, 2007·International Journal of Colorectal Disease·Peter FelderbauerPeter Hoffmann
Jul 17, 2007·American Journal of Physiology. Lung Cellular and Molecular Physiology·Nguyen Thu Ngan TrinhEmmanuelle Brochiero
Nov 10, 2007·American Journal of Physiology. Gastrointestinal and Liver Physiology·Rebecca S DiseD Brent Polk
Jan 18, 2008·World Journal of Gastroenterology : WJG·Andreas Sturm, Axel U Dignass
Jul 16, 2008·Inflammatory Bowel Diseases·Michael A McGuckinGraham Radford-Smith
Aug 14, 2008·Physiology·Albrecht SchwabChristian Stock
Sep 2, 2008·American Journal of Physiology. Lung Cellular and Molecular Physiology·Nguyen Thu Ngan TrinhEmmanuelle Brochiero
Jan 9, 2009·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Michel A BoivinThomas Y Ma

❮ Previous
Next ❯

Citations

Sep 29, 2018·International Journal of Molecular Sciences·Miki MatsuiSusumu Ohya
Oct 19, 2016·Pflügers Archiv : European journal of physiology·B BonitoI Novak
May 14, 2018·The American Journal of the Medical Sciences·Corey J KetchemLevi J Beverly
Dec 17, 2020·American Journal of Physiology. Cell Physiology·Dina CosmeFernando Magro

❮ Previous
Next ❯

Methods Mentioned

BETA
IEC
FCS
electrophoresis
biopsies
PCR

Software Mentioned

AxioVision
MAGIX
SDS
ImageJ
GraphPad Prism
Image Quant

Related Concepts

Related Feeds

Cell Migration

Cell migration is involved in a variety of physiological and pathological processes such as embryonic development, cancer metastasis, blood vessel formation and remoulding, tissue regeneration, immune surveillance and inflammation. Here is the latest research.

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.