Necrotizing enterocolitis in a mouse model leads to widespread renal inflammation, acute kidney injury, and disruption of renal tight junction proteins.
Necrotizing enterocolitis in a mouse model leads to widespread renal inflammation, acute kidney injury, and disruption of renal tight junction proteins.
复制标题
DOI：
10.1038/pr.2015.146
复制
发表时间：
2015-11
影响因子：
3.6
通讯作者：
Chen YH
中科院分区：
文献类型：
--
作者：
Garg PM;Tatum R;Ravisankar S;Shekhawat PS;Chen YH
坏死性小肠结肠炎 (NEC) 是一种影响早产儿的破坏性疾病，导致高死亡率和慢性发病率。严重的 NEC 与急性肾功能衰竭、体液失衡、低钠血症和酸中毒有关。我们使用 NEC 小鼠模型研究了 NEC 对肾脏紧密连接 (TJ) 蛋白的影响，以研究观察到的肾功能障碍的基础。通过配方奶喂养并使 C57BL/6 小鼠经历一段时期的缺氧和冷应激来诱导 NEC。 NEC 通过肉眼和组织学检查确诊。我们研究了肾脏炎症的各种标志物，并使用免疫荧光染色和蛋白质印迹研究了几种 TJ 蛋白和 AQP2 表达的变化。我们发现 NEC 肾脏中 NFκB、TGFβ 和 ERK1/2 以及 Claudin-1、-2、-3、-4、-8 和 AQP-2 的表达显着增加。 NEC 肾脏中claudin-2 的膜定位发生改变，并且 TJ 处的免疫染色信号被破坏。 NEC 不仅会导致肠道出现严重的炎症反应，还会导致肾脏出现严重的炎症反应。 NEC 增加了几种 TJ 蛋白的表达，并导致肾小管中claudin-2 的破坏。这些观察到的变化可以帮助解释 NEC 中观察到的一些临床发现。
Necrotizing enterocolitis (NEC) is a devastating condition affecting premature infants and leads to high mortality and chronic morbidity. Severe form of NEC is associated with acute renal failure, fluid imbalance, hyponatremia and acidosis. We investigated the effect of NEC on tight junction (TJ) proteins in kidneys using a NEC mouse model to investigate the basis for the observed renal dysfunction. NEC was induced in C57BL/6 mice by formula feeding and subjecting them to periods of hypoxia and cold stress. NEC was confirmed by gross and histological examination. We studied various markers of inflammation in kidneys and investigated changes in expression of several TJ proteins and AQP2 using immunofluorecent staining and Western blotting. We found markedly increased expression of NFκB, TGFβ and ERK1/2 along with claudin-1, -2, -3, -4, -8 and AQP-2 in NEC kidneys. The membrane localization of claudin-2 was altered in the NEC kidneys and its immunostaining signal at TJ was disrupted. NEC led to a severe inflammatory response not only in the gut but also the kidneys. NEC increased expression of several TJ proteins and caused disruption of claudin-2 in renal tubules. These observed changes can help explain some of the clinical findings observed in NEC.