Jiangsu Institute of Hematology, The First Affiliated Hospital and Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Protection, Suzhou Medical College, Soochow University, Suzhou, China; Cyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Prevention, Soochow University, Suzhou, China.
Cyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Prevention, Soochow University, Suzhou, China.
Life Sci. 2024 Feb 15;339:122446. doi: 10.1016/j.lfs.2024.122446. Epub 2024 Jan 19.
High dietary salt consumption is a risk factor for inflammatory bowel disease (IBD). Corin is a protease that activates atrial natriuretic peptide (ANP), thereby regulating sodium homeostasis. Corin acts in multiple tissues, including the intestine. In mice, corin deficiency impairs intestinal sodium excretion. This study aims to examine if reduced intestinal sodium excretion alters the pathophysiology of IBD.
Wild-type (WT), Corin knockout (KO), and Corin kidney conditional KO (kcKO) mice were tested in a colitis model induced by dextran sulfide sodium (DSS). Effects of ANP on DSS-induced colitis were tested in WT and Corin KO mice. Body weight changes in the mice were monitored. Necropsy, histological analysis, and immunostaining studies were conducted to examine colon length and mucosal lesions. Fecal sodium levels were measured. RT-PCR was done to analyze proinflammatory genes in colon samples.
DSS-treated Corin KO mice had an ameliorated colitis phenotype with less body weight loss, longer colon lengths, smaller mucosal lesions, lower disease scores, more preserved goblet cells, and suppressed proinflammatory genes in the colon. In longitudinal studies, the DSS-treated Corin KO mice had delayed onset of colon mucosal lesions. ANP administration lessened the colitis in WT, but not Corin KO, mice. Analyses of WT, Corin KO, and Corin kcKO mice indicated that fecal sodium excretion, controlled by intestinal corin, may regulate inflammatory responses in DSS-induced colitis in mice.
Our findings indicate a role of corin in intestinal pathophysiology, suggesting that reduced intestinal sodium level may offer protective benefits against IBD.
高盐饮食是炎症性肠病（IBD）的一个风险因素。膜联蛋白酶 Corin 可激活心钠肽（ANP），从而调节钠稳态。Corin 在包括肠道在内的多种组织中发挥作用。在小鼠中，Corin 缺乏会损害肠道钠排泄。本研究旨在研究肠道钠排泄减少是否会改变 IBD 的病理生理学。
在葡聚糖硫酸钠（DSS）诱导的结肠炎模型中，对野生型（WT）、Corin 敲除（KO）和 Corin 肾条件性敲除（kcKO）小鼠进行了测试。在 WT 和 Corin KO 小鼠中测试了 ANP 对 DSS 诱导的结肠炎的影响。监测小鼠的体重变化。进行尸检、组织学分析和免疫染色研究，以检查结肠长度和黏膜病变。测量粪便中钠的水平。通过 RT-PCR 分析结肠样本中的促炎基因。
用 DSS 处理的 Corin KO 小鼠具有改善的结肠炎表型，体重减轻较少，结肠较长，黏膜病变较小，疾病评分较低，杯状细胞保存较好，结肠中促炎基因受到抑制。在纵向研究中，用 DSS 处理的 Corin KO 小鼠的结肠黏膜病变发生较晚。ANP 给药减轻了 WT 小鼠的结肠炎，但对 Corin KO 小鼠没有作用。对 WT、Corin KO 和 Corin kcKO 小鼠的分析表明，肠道 Corin 控制的粪便钠排泄可能调节 DSS 诱导的结肠炎中的炎症反应。
我们的研究结果表明 Corin 在肠道病理生理学中的作用，表明肠道钠水平降低可能对 IBD 具有保护作用。
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