KCNN4 Expression Is Elevated in Inflammatory Bowel Disease: This Might Be a Novel Marker and Therapeutic Option Targeting Potassium Channels
| Autor: | K Gülow, Martina Müller, C Kunst, Gisela Wölfel, Kirstin Pollinger, Christoph Süss, Lucile Broncy |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Adult Male Cell Inflammation digestive system Inflammatory bowel disease Permeability Cell Line 03 medical and health sciences KCNN4 0302 clinical medicine Western blot Crohn Disease Membrane Transport Modulators Medicine Animals Humans Benzothiazoles Molecular Targeted Therapy Intestinal Mucosa Aged Crohn's disease medicine.diagnostic_test business.industry Gastroenterology Diverticulitis Middle Aged medicine.disease Intermediate-Conductance Calcium-Activated Potassium Channels Ulcerative colitis digestive system diseases Rats Up-Regulation 030104 developmental biology medicine.anatomical_structure Case-Control Studies Cancer research 030211 gastroenterology & hepatology Benzimidazoles Colitis Ulcerative Female medicine.symptom business |
| Zdroj: | Journal of gastrointestinal and liver diseases : JGLD. 29(4) |
| ISSN: | 1842-1121 |
| Popis: | Background and Aims: The K + channel KCNN4 is involved in many inflammatory diseases. Previous work has shown that this channel is involved in epithelial ion transport and intestinal restitution. In inflammatory bowel diseases (IBD) a defective epithelial barrier can lead to typical symptoms like secretory diarrhea and the formation of intestinal ulcers. We compared surgical samples from patients with IBD, diverticulitis and controls without inflammation to determine the potential role of KCNN4 as a diagnostic marker and/or therapeutic target. Methods: mRNA-levels of KCNN4 and a control K + channel were determined in intestinal epithelial cells (IEC) from patients with IBD, diverticulitis and controls. In addition, we performed a Western blot analysis of KCNN4 and a respective control K + channel in IEC from patients with IBD. Furthermore, we determined epithelial barrier integrity by measuring the flux of fluorescent-labeled dextran beads across a cell monolayer upon incubation with interferon-γ. Results: KCNN4 mRNA and protein levels were elevated in IEC from patients with Crohn`s disease (CD) and ulcerative colitis (UC). Of note, KCNN4 was not elevated in non-IBD intestinal inflammatory conditions e.g. diverticulitis. Of clinical relevance, pharmacological KCNN4 channel openers stabilized epithelial barrier function in vitro. Thus, KCNN4 may have a protective role in IBD and constitute a therapeutic target. Conclusions: Our data demonstrate elevated KCNN4 both at mRNA and protein level in IEC specifically from patients with IBD. Therefore, we conclude that KCNN4 could be used as a novel marker for IBD, especially for the establishment of initial diagnosis. Of therapeutic consequence, we show that pharmacological KCNN4 openers stabilize the epithelial barrier. Thus, KCNN4 might be a novel target to diagnose and treat IBD. |
| Databáze: | OpenAIRE |
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