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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

Digestive system malignancies are the most common cancer types worldwide and exhibit an extremely low overall 5-year survival rate. Therefore, clinically applicable biomarkers for predicting clinical outcome are urgently required. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is abnormally expressed in several cancer types. However, to the best of our knowledge, the association between MALAT1 expression and the prognosis of digestive system malignancies remains unknown. Therefore, the current study performed a meta-analysis to comprehensively summarize the association between MALAT1 expression and digestive system malignancies. A total of 1,157 Asian patients from 12 eligible studies [eight studies that investigated overall survival (OS), two studies that investigated disease-free survival and two studies that investigated both indicators] were analyzed. The present results identified a significant association between MALAT1 abundance and poor OS in patients with digestive system malignancies, with a pooled hazard ratio (HR) of 1.62 [95% confidence interval (CI), 1.35–1.88; P<0.001]. The tumor type, region, sample size and analysis type did not alter the predictive value of MALAT1 as an independent factor for survival. Furthermore, MALAT1 overexpression was an unfavorable prognostic factor for the overall survival of patients with esophageal carcinoma, pancreatic cancer, hepatocellular carcinoma and gastric cancer, with HRs of 1.89 (95% CI, 1.29–2.49), 1.76 (95% CI, 0.89–2.63), 1.46 (95% CI, 0.76–2.17) and 1.41 (95% CI, 1.04–1.78), respectively. In particular, increased MALAT1 expression levels were significantly associated with decreased OS in patients with colorectal cancer (HR, 3.04; 95% CI, 1.77–4.31). In conclusion, lncRNA MALAT1 may be a potential prognostic factor for digestive system malignancies in Asian populations.

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