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miR-199a-5p Exacerbated Intestinal Barrier Dysfunction through Inhibiting Surfactant Protein D and Activating NF-κB Pathway in Sepsis.
Mediators of Inflammation ( IF 4.6 ) Pub Date : 2020-05-18 , DOI: 10.1155/2020/8275026
Xianjin Du 1 , Dan Tian 1 , Jie Wei 1 , Chen Yan 1 , Peng Hu 1 , Xu Wu 1 , Wenbin Yang 1 , Zhanyong Zhu 2
Affiliation  

Sepsis is a severe disease, which results from the excessive inflammatory response to the infection. Dysfunction of intestinal barrier is a crucial problem in various pathological conditions. Meanwhile, microRNAs exhibit significant roles in the modulation of many diseases, including sepsis. Multiple investigations indicate that miR-199a-5p participates in different human diseases. Nevertheless, little is known on the roles of miR-199a-5p in sepsis. Herein, we evaluated the mechanism of miR-199a-5p on the intestinal barrier dysfunction in sepsis. Intestinal mucosa permeability indicators including D-lactic acid, DAO, and FD-40 levels were determined, and they were greatly increased in sepsis. Then, we proved that miR-199a-5p was induced in sepsis mice tissues and isolated intestinal epithelial cells. Moreover, miR-199a-5p increased D-lactic acid, DAO, and FD-40 while inhibition of miR-199a-5p exhibited a reversed process. Additionally, we observed that miR-199a-5p affected the oxidative damage and inflammation in the intestine tissues from sepsis mice. The content of MDA was elevated whereas SOD was remarkably repressed in the miR-199a-5p mimic group. IL-6, IL-1β, and TNF-α were induced by miR-199a-5p overexpression while IL-10 was reduced by miR-199a-5p. Subsequently, surfactant protein D (SP-D) was predicted as the target of miR-199a-5p. The activation of NF-κB has been identified in sepsis. Herein, we demonstrated that inhibitor of miR-199a-5p contributed to IEC injury via targeting SP-D and inactivating the NF-κB pathway. These revealed miR-199a-5p exacerbated the intestinal barrier dysfunction via inhibiting SP-D and activating the NF-κB pathway in sepsis.

中文翻译:

miR-199a-5p通过抑制脓毒症中的表面活性蛋白D和激活NF-κB途径加剧了肠道屏障功能障碍。

败血症是一种严重的疾病,是由对感染的过度炎症反应导致的。肠屏障功能障碍是各种病理条件下的关键问题。同时,microRNA在许多疾病(包括败血症)的调节中发挥重要作用。多项研究表明,miR-199a-5p参与了不同的人类疾病。然而,关于miR-199a-5p在败血症中的作用还知之甚少。在本文中,我们评估了miR-199a-5p对败血症中肠屏障功能障碍的作用机制。测定了肠粘膜通透性指标,包括D-乳酸,DAO和FD-40的水平,并在败血症中大大增加。然后,我们证明了在脓毒症小鼠组织和分离的肠上皮细胞中诱导了miR-199a-5p。而且,miR-199a-5p增加了D-乳酸,DAO和FD-40在抑制miR-199a-5p时表现出相反的过程。此外,我们观察到miR-199a-5p影响败血症小鼠肠道组织的氧化损伤和炎症。在miR-199a-5p模拟组中,MDA含量升高,而SOD显着降低。IL-6,IL-1miR-199a-5p过表达诱导β和TNF- α,而miR-199a-5p降低IL-10。随后,预测表面活性剂蛋白D(SP-D)作为miR-199a-5p的靶标。NF-κB的激活κ B已经在败血症已确定。在本文中,我们证明的miR-199a的-5P经由靶向SP-d和灭活NF-促成IEC损伤的该抑制剂κ乙通路。这些揭示的miR-199a的-5P加剧通过抑制SP-d和激活NF-肠屏障功能障碍κ乙通路在败血症。
更新日期:2020-05-18
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