P048 Decreased expression of aquaporins in colonic biopsies from collagenous colitis patients. A novel diarrhoeal pathomechanism?

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Abstract

Background: Collagenous colitis (CC) is an inflammatory bowel disease and common cause for watery diarrhoea. The diarrhoeal mechanisms in CC are poorly understood as well as the mode of action how budesonide effectively reduces stool frequency and improves stool consistency. Aquaporins are water channels responsible for absorption and water balance in the colon as well as water homeostasis inside cells. We therefore investigated aquaporins expression in colonic biopsies of CC patients with active disease and in clinical remission under budesonide therapy.

Methods: The aquaporin expression was assessed using qPCR on colonic biopsies. The aquaporins investigated were AQP1, AQP3, AQP4, AQP6, AQP7, AQP8, AQP9, AQP10 and AQP11. We also investigated the sodium/ hydrogen exchanger 1 (NHE1). Further investigation with immunohistochemistry is ongoing.

Results: qPCR analysis of the colonic biopsies revealed a significant decrease in the mRNA expression of AQP1, AQP8, AQP11 and NHE1 in CC-patients compared to healthy controls. Under budesonide therapy which led to clinical remission in all patients, we observed an increase in the expressions of all AQPs, especially significant for AQP8 and NHE1 compared to prior treatment.

Conclusions: CC patients showed a decreased expression level of AQP1, 8, 11 and NHE1 compared to healthy controls. During budesonide treatment the expression was re-established for AQP1 and 11 and significantly increased for AQP8 and NHE1 indicating an involvement of AQPs in CC. AQP dysregulation could be a novel pathomechanism to explain the watery diarrhoea in CC and budesonide might have anti-diarrhoeal properties via AQP upregulation.

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