Aquaporin 4 deficiency alleviates experimental colitis in mice
Aquaporin 4 deficiency alleviates experimental colitis in mice
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水通道蛋白 4 缺乏可减轻小鼠实验性结肠炎
DOI：
10.1096/fj.201802769rr
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发表时间：
2019-08-01
期刊：
影响因子：
4.8
通讯作者：
Shen, Lizong
中科院分区：
文献类型：
--
作者：
Wang, Liuhua;Tang, Hua;Shen, Lizong
水通道蛋白（AQP）4表达于结肠上皮细胞的基底膜，本研究旨在探讨AQP 4在实验性结肠炎中的作用机制。通过口服葡聚糖硫酸钠（DSS）在AQP 4敲除（AQP 4（-/-））CD-1小鼠和AQP 4野生型（AQP 4（wt））小鼠中诱导实验性结肠炎。实验性结肠炎在临床上建立。与AQP 4（wt）小鼠相比，AQP 4（-/-）小鼠对DSS诱导的实验性结肠炎表现出更高的耐受性，包括更小程度的体重减轻、腹泻和出血、更低的疾病活动指数评分、更长的结肠长度和更少的组织学评分。DSS处理的AQP 4（-/-）小鼠血清IL-6和TNF水平较低，IL-10水平较高，炎性细胞浸润较少。DSS处理的AQP 4（-/-）小鼠也具有较低的NF-κ B p65免疫染色以及p65和磷酸化p65的核水平。16 S rRNA测序结果表明，DSS处理的AQP 4（-/-）小鼠保持肠道微生物多样性，并具有较高的厚壁菌门/拟杆菌门比例和较高的丹毒丝菌科物种的相对丰度。这些结果首次表明，AQP 4缺乏加重了小鼠实验性结肠炎。我们的研究有助于了解炎症性肠病的发病机制，阻断AQP 4可能是溃疡性结肠炎的一种新的治疗方法。Wang，L.，美国，唐，H.，Wang，C.，中国地质大学，Hu，Y.，王，S.，申湖，澳-地水通道蛋白4缺乏导致小鼠实验性结肠炎。
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 (AQP4(wt)) mice by oral administration of dextran sulfate sodium (DSS). Experimental colitis was clinically established. Compared with AQP4(wt) 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-kappa B 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.