Aquaporin 4 deficiency alleviates experimental colitis in mice

Abstract

Aquaporin (AQP) 4 is expressed in the basolateral membrane of colonic epithelial cells, and the purpose of this study was to explore the mechanistic role of AQP4 in experimental colitis. Experimental colitis was induced in AQP4 knockout (AQP4−/−) CD‐1 mice and AQP4 wild‐type (AQP4wt) mice by oral administration of dextran sulfate sodium (DSS). Experimental colitis was clinically established. Compared with AQP4wt mice, AQP4−/− mice showed increased tolerance to DSS‐induced experimental colitis, including lesser degree of weight loss, diarrhea and bleeding, lower disease activity index scores, longer colon lengths, and lesser histologic scores. DSS‐treated AQP4−/− mice had lower serum levels of IL‐6 and TNF, higher IL‐10 level, and lesser inflammatory cell infiltration. DSS‐treated AQP4−/− mice also had lower immunostaining of NF‐κB p65 as well as nuclear levels of p65 and phosphorylated p65. Sequencing of 16S rRNA indicated that DSS‐treated AQP4−/− mice maintained intestinal microbial diversity and had higher Firmicutes/Bacteroidetes ratios and greater relative abundance of Erysipelotrichaceae species. These results suggested for the first time that AQP4 deficiency alleviates experimental colitis in mice. Our study helps to understand the pathogenesis of inflammatory bowel diseases, and blocking AQP4 may represent a novel therapeutic approach for ulcerative colitis.—Wang, L., Tang, H., Wang, C., Hu, Y., Wang, S., Shen, L. Aquaporin 4 deficiency alleviates experimental colitis in mice. FASEB J. 33, 8935–8944 (2019). http://www.fasebj.org

Maternal Lactobacillus reuteri supplementation shifts the intestinal microbiome in mice and provides protection from experimental colitis in female offspring

“…In the validation cohort, when mice were reared in the same room of our small vivarium, stochastic microbiome variation influencing DSS susceptibility was Faecalibaculum has been rarely associated with DSS sensitivity in certain mouse strains. 33 These findings corroborate prior observations on small vivarium-induced relative DSS resistance in mice, compared to large vendor bred animals 27 and implicate Faecalibaculum to have participated in the vendor-originated increase in colitis severity variation of our work. Our results also showed that the convergence of gut microbiomes in a smaller vivarium compared to a large vendor is associated with a reduction in random murine DSS sensitivity.…”

MTA1 aggravates experimental colitis in mice by promoting transcription factor HIF1A and up-regulating AQP4 expression

“…Aquaporin 4 (AQP4) is considered as a type of transmembrane protein originating from the aquaporin family, and further serves as a vital water channel in the mammalian brain [ 12 ]. As previously reported, deficiency in AQP4 can facilitate the attenuation of experimental colitis in mouse models [ 13 ]. In light of the aforementioned literature, we speculated that MTA1 could potentially influence the development of experimental colitis with regulation of the HIF1A/AQP4 axis and subsequently performed a series of experiments to validate the same, in an effort to uncover novel diagnostic and therapeutic modalities against experimental colitis.…”

GPA Peptide-Induced Nur77 Localization at Mitochondria Inhibits Inflammation and Oxidative Stress through Activating Autophagy in the Intestine

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