Nattramilarasu, Praveen Kumar ORCID: 0000-0002-8212-7368, Buecker, Roland, de Sa, Fabia Daniela Lobo, Fromm, Anja, Nagel, Oliver, Lee, In-Fah Maria, Butkevych, Eduard, Mousavi, Soraya, Genger, Claudia, Klove, Sigri, Heimesaat, Markus M., Bereswill, Stefan, Schweiger, Michal R., Nielsen, Hans Linde, Troeger, Hanno and Schulzke, Joerg-Dieter (2020). Campylobacter concisus Impairs Sodium Absorption in Colonic Epithelium via ENaC Dysfunction and Claudin-8 Disruption. Int. J. Mol. Sci., 21 (2). BASEL: MDPI. ISSN 1422-0067

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Abstract

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 beta- and gamma-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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Nattramilarasu, Praveen KumarUNSPECIFIEDorcid.org/0000-0002-8212-7368UNSPECIFIED
Buecker, RolandUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
de Sa, Fabia Daniela LoboUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fromm, AnjaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nagel, OliverUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lee, In-Fah MariaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Butkevych, EduardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mousavi, SorayaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Genger, ClaudiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Klove, SigriUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heimesaat, Markus M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bereswill, StefanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schweiger, Michal R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nielsen, Hans LindeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Troeger, HannoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schulzke, Joerg-DieterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-349279
DOI: 10.3390/ijms21020373
Journal or Publication Title: Int. J. Mol. Sci.
Volume: 21
Number: 2
Date: 2020
Publisher: MDPI
Place of Publication: BASEL
ISSN: 1422-0067
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
MICE LACKING; BACTEROIDES-GRACILIS; EIKENELLA-CORRODENS; TETRAZOLIUM SALT; BARRIER FUNCTION; WOLINELLA-RECTA; NA+ ABSORPTION; EXPRESSION; CHANNEL; INTESTINEMultiple languages
Biochemistry & Molecular Biology; Chemistry, MultidisciplinaryMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/34927

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