Campylobacter concisus Impairs Sodium Absorption in Colonic Epithelium via ENaC Dysfunction and Claudin-8 Disruption.

Autor:	Nattramilarasu PK; Institute of Clinical Physiology/Nutritional Medicine, Medical Department, Division of Gastroenterology, Infectiology and Rheumatology, Charité-Universitätsmedizin Berlin, 12203 Berlin, Germany., Bücker R; Institute of Clinical Physiology/Nutritional Medicine, Medical Department, Division of Gastroenterology, Infectiology and Rheumatology, Charité-Universitätsmedizin Berlin, 12203 Berlin, Germany., Lobo de Sá FD; Institute of Clinical Physiology/Nutritional Medicine, Medical Department, Division of Gastroenterology, Infectiology and Rheumatology, Charité-Universitätsmedizin Berlin, 12203 Berlin, Germany., Fromm A; Institute of Clinical Physiology/Nutritional Medicine, Medical Department, Division of Gastroenterology, Infectiology and Rheumatology, Charité-Universitätsmedizin Berlin, 12203 Berlin, Germany., Nagel O; Institute of Clinical Physiology/Nutritional Medicine, Medical Department, Division of Gastroenterology, Infectiology and Rheumatology, Charité-Universitätsmedizin Berlin, 12203 Berlin, Germany., Lee IM; Institute of Clinical Physiology/Nutritional Medicine, Medical Department, Division of Gastroenterology, Infectiology and Rheumatology, Charité-Universitätsmedizin Berlin, 12203 Berlin, Germany., Butkevych E; Institute of Clinical Physiology/Nutritional Medicine, Medical Department, Division of Gastroenterology, Infectiology and Rheumatology, Charité-Universitätsmedizin Berlin, 12203 Berlin, Germany., Mousavi S; Institute of Microbiology, Infectious Diseases and Immunology, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, 14195 Berlin, Germany., Genger C; Institute of Microbiology, Infectious Diseases and Immunology, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, 14195 Berlin, Germany., Kløve S; Institute of Microbiology, Infectious Diseases and Immunology, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, 14195 Berlin, Germany., Heimesaat MM; Institute of Microbiology, Infectious Diseases and Immunology, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, 14195 Berlin, Germany., Bereswill S; Institute of Microbiology, Infectious Diseases and Immunology, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, 14195 Berlin, Germany., Schweiger MR; Laboratory for Epigenetics and Tumour genetics, University Hospital Cologne and Centre for Molecular Medicine Cologne, 50931 Cologne, Germany., Nielsen HL; Department of Clinical Microbiology, Aalborg University Hospital, 9000 Aalborg, Denmark.; Department of Clinical Medicine, Aalborg University, 9000 Aalborg, Denmark., Troeger H; Medical Department, Division of Gastroenterology, Infectiology and Rheumatology, Charité-Universitätsmedizin Berlin, 12203 Berlin, Germany., Schulzke JD; Institute of Clinical Physiology/Nutritional Medicine, Medical Department, Division of Gastroenterology, Infectiology and Rheumatology, Charité-Universitätsmedizin Berlin, 12203 Berlin, Germany.
Jazyk:	angličtina
Zdroj:	International journal of molecular sciences [Int J Mol Sci] 2020 Jan 07; Vol. 21 (2). Date of Electronic Publication: 2020 Jan 07.
DOI:	10.3390/ijms21020373
Abstrakt:	The epithelial sodium channel (ENaC) can increase the colonic absorptive capacity for salt and water. Campylobacter concisus is a common pathogenic epsilonproteobacterium, causing enteritis and diarrhea. It can induce barrier dysfunction in the intestine, but its influence on intestinal transport function is still unknown. Therefore, our study aimed to characterize C. concisus effects on ENaC using the HT-29/B6-GR/MR (epithelial cell line HT-29/B6 transfected with glucocorticoid and mineralocorticoid receptors) cell model and mouse colon. In Ussing chambers, C. concisus infection inhibited ENaC-dependent Na + transport as indicated by a reduction in amiloride-sensitive short circuit current (-55%, n = 15, p < 0.001). This occurred via down-regulation of β- and γ-ENaC mRNA expression and ENaC ubiquitination due to extracellular signal-regulated kinase (ERK)1/2 activation, predicted by Ingenuity Pathway Analysis (IPA). In parallel, C. concisus reduced the expression of the sealing tight junction (TJ) protein claudin-8 and induced claudin-8 redistribution off the TJ domain of the enterocytes, which facilitates the back leakage of Na + ions into the intestinal lumen. In conclusion, C. concisus caused ENaC dysfunction via interleukin-32-regulated ERK1/2, as well as claudin-8-dependent barrier dysfunction-both of which contribute to Na + malabsorption and diarrhea.
Databáze:	MEDLINE
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