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Article

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

1
Institute of Clinical Physiology/Nutritional Medicine, Medical Department, Division of Gastroenterology, Infectiology and Rheumatology, Charité—Universitätsmedizin Berlin, 12203 Berlin, Germany
2
Institute of Microbiology, Infectious Diseases and Immunology, Charité—Universitätsmedizin Berlin, Campus Benjamin Franklin, 14195 Berlin, Germany
3
Laboratory for Epigenetics and Tumour genetics, University Hospital Cologne and Centre for Molecular Medicine Cologne, 50931 Cologne, Germany
4
Department of Clinical Microbiology, Aalborg University Hospital, 9000 Aalborg, Denmark
5
Department of Clinical Medicine, Aalborg University, 9000 Aalborg, Denmark
6
Medical Department, Division of Gastroenterology, Infectiology and Rheumatology, Charité—Universitätsmedizin Berlin, 12203 Berlin, Germany
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(2), 373; https://doi.org/10.3390/ijms21020373
Received: 1 November 2019 / Revised: 31 December 2019 / Accepted: 31 December 2019 / Published: 7 January 2020
(This article belongs to the Special Issue Ion and Molecule Transport in Membrane Systems 2.0)
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. View Full-Text
Keywords: sodium transport; epithelial sodium channel, extracellular signal-regulated kinase, Campylobacter concisus; diarrhea; tight junction; claudin-8 sodium transport; epithelial sodium channel, extracellular signal-regulated kinase, Campylobacter concisus; diarrhea; tight junction; claudin-8
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MDPI and ACS Style

Nattramilarasu, P.K.; Bücker, R.; Lobo de Sá, F.D.; Fromm, A.; Nagel, O.; Lee, I.-F.M.; Butkevych, E.; Mousavi, S.; Genger, C.; Kløve, S.; Heimesaat, M.M.; Bereswill, S.; Schweiger, M.R.; Nielsen, H.L.; Troeger, H.; Schulzke, J.-D. Campylobacter concisus Impairs Sodium Absorption in Colonic Epithelium via ENaC Dysfunction and Claudin-8 Disruption. Int. J. Mol. Sci. 2020, 21, 373. https://doi.org/10.3390/ijms21020373

AMA Style

Nattramilarasu PK, Bücker R, Lobo de Sá FD, Fromm A, Nagel O, Lee I-FM, Butkevych E, Mousavi S, Genger C, Kløve S, Heimesaat MM, Bereswill S, Schweiger MR, Nielsen HL, Troeger H, Schulzke J-D. Campylobacter concisus Impairs Sodium Absorption in Colonic Epithelium via ENaC Dysfunction and Claudin-8 Disruption. International Journal of Molecular Sciences. 2020; 21(2):373. https://doi.org/10.3390/ijms21020373

Chicago/Turabian Style

Nattramilarasu, Praveen K., Roland Bücker, Fábia D. Lobo de Sá, Anja Fromm, Oliver Nagel, In-Fah M. Lee, Eduard Butkevych, Soraya Mousavi, Claudia Genger, Sigri Kløve, Markus M. Heimesaat, Stefan Bereswill, Michal R. Schweiger, Hans L. Nielsen, Hanno Troeger, and Jörg-Dieter Schulzke. 2020. "Campylobacter concisus Impairs Sodium Absorption in Colonic Epithelium via ENaC Dysfunction and Claudin-8 Disruption" International Journal of Molecular Sciences 21, no. 2: 373. https://doi.org/10.3390/ijms21020373

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