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The Water Channel A...
The Water Channel Aquaporin 8 is a Critical Regulator of Intestinal Fluid Homeostasis in Collagenous Colitis
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- Escudero-Hernández, Celia (författare)
- Linköpings universitet,Avdelningen för molekylär medicin och virologi,Medicinska fakulteten
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- Münch, Andreas, 1970- (författare)
- Linköpings universitet,Avdelningen för molekylär medicin och virologi,Medicinska fakulteten,Region Östergötland, Mag- tarmmedicinska kliniken
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- Østvik, Ann-Elisabet (författare)
- Norwegian University of Science and Technology (NTNU), Trondheim, Norway; St Olav’s University Hospital, Trondheim, Norway
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- Granlund, Atle van Beelen (författare)
- Norwegian University of Science and Technology (NTNU), Trondheim, Norway; St Olav’s University Hospital, Trondheim, Norway
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- Koch, Stefan, 1977- (författare)
- Linköpings universitet,Avdelningen för molekylär medicin och virologi,Medicinska fakulteten,Wallenberg Centre for Molecular Medicine (WCMM)
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(creator_code:org_t)
- 2020-02-04
- 2020
- Engelska.
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Ingår i: Journal of Crohn's & Colitis. - : Oxford University Press. - 1873-9946 .- 1876-4479. ; 14:7, s. 962-973
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https://doi.org/10.1...
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https://liu.diva-por... (primary) (Raw object)
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https://urn.kb.se/re...
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Abstract
Ämnesord
Stäng
- BACKGROUND AND AIMS: Diarrhoea is a common, debilitating symptom of gastrointestinal disorders. Pathomechanisms probably involve defects in trans-epithelial water transport, but the role of aquaporin [AQP] family water channels in diarrhoea-predominant diseases is unknown. We investigated the involvement of AQPs in the pathobiology of collagenous colitis [CC], which features chronic, watery diarrhoea despite overtly normal intestinal epithelial cells [IECs].METHODS: We assessed the expression of all AQP family members in mucosal samples of CC patients before and during treatment with the corticosteroid drug budesonide, steroid-refractory CC patients and healthy controls. Samples were analysed by genome-wide mRNA sequencing [RNA-seq] and quantitative real-time PCR [qPCR]. In some patients, we performed tissue microdissection followed by RNA-seq to explore the IEC-specific CC transcriptome. We determined changes in the protein levels of the lead candidates in IEC by confocal microscopy. Finally, we investigated the regulation of AQP expression by corticosteroids in model cell lines.RESULTS: Using qPCR and RNA-seq, we identified loss of AQP8 expression as a hallmark of active CC, which was reverted by budesonide treatment in steroid-responsive but not refractory patients. Consistently, decreased AQP8 mRNA and protein levels were observed in IECs of patients with active CC, and steroid drugs increased AQP8 expression in model IECs. Moreover, low APQ8 expression was strongly associated with higher stool frequency in CC patients.CONCLUSION: Down-regulation of epithelial AQP8 may impair water resorption in active CC, resulting in watery diarrhoea. Our results suggest that AQP8 is a potential drug target for the treatment of diarrhoeal disorders.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Nyckelord
- Microscopic colitis
- RNA sequencing
- permeability
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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