dc.contributor.author
Nattramilarasu, Praveen Kumar
dc.contributor.author
Bücker, Roland
dc.contributor.author
Lobo de Sá, Fábia Daniela
dc.contributor.author
Fromm, Anja
dc.contributor.author
Nagel, Oliver
dc.contributor.author
Lee, In-Fah Maria
dc.contributor.author
Butkevych, Eduard
dc.contributor.author
Mousavi, Soraya
dc.contributor.author
Genger, Claudia
dc.contributor.author
Kløve, Sigri
dc.contributor.author
Heimesaat, Markus M.
dc.contributor.author
Bereswill, Stefan
dc.contributor.author
Schweiger, Michal R.
dc.contributor.author
Nielsen, Hans Linde
dc.contributor.author
Troeger, Hanno
dc.contributor.author
Schulzke, Jörg-Dieter
dc.date.accessioned
2020-01-27T15:14:48Z
dc.date.available
2020-01-27T15:14:48Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/26523
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-26283
dc.description.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 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.
en
dc.rights.uri
https://creativecommons.org/licenses/by/4.0/
dc.subject
sodium transport
en
dc.subject
epithelial sodium channel
en
dc.subject
extracellular signal-regulated kinase
en
dc.subject
Campylobacter concisus
de
dc.subject
tight junction
en
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit
dc.title
Campylobacter concisus Impairs Sodium Absorption in Colonic Epithelium via ENaC Dysfunction and Claudin-8 Disruption
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation.articlenumber
373
dcterms.bibliographicCitation.doi
10.3390/ijms21020373
dcterms.bibliographicCitation.journaltitle
International Journal of Molecular Sciences
dcterms.bibliographicCitation.number
2
dcterms.bibliographicCitation.originalpublishername
MDPI AG
dcterms.bibliographicCitation.volume
21
refubium.affiliation
Charité - Universitätsmedizin Berlin
refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.bibliographicCitation.pmid
31936044
dcterms.isPartOf.eissn
1422-0067