长链非编码RNA-KIF9-AS1调控肠上皮蛋白syndecan-1在溃疡性结肠炎肠粘膜屏障维护中的作用机制研究

溃疡性结肠炎（ulcerative colitis，UC）是炎症性肠病的一种，目前病因不明且缺乏有效的治疗及预防手段。我们的前期研究表明肠上皮蛋白Syndecan-1(Sdc1)是UC发病中的关键蛋白且对肠粘膜屏障具有保护作用，但是Sdc1上游调控领域目前研究较少。lncRNA在蛋白转录翻译过程发挥了至关重要的作用，我们通过生物信息学分析及预测发现，Sdc1可能是KIF9-AS1的潜在靶标且二者存在相关关系。因此我们提出UC肠粘膜损伤及发病新的机制：在炎症刺激下，KIF9-AS1启动转录靶向抑制Sdc1，破坏肠粘膜屏障功能，活化炎性因子及炎症通路引起UC；抑制KIF9-AS1/Sdc1轴可能发挥防治UC的保护作用。我们将采用炎症模型构建、过表达、RNA干扰等方法，以及ChIP和双荧光素酶报告基因实验等分子生物学手段，从体内及体外对这一假说进行探讨，为疾病防治寻找新的治疗靶点及新的干预途径。

Ulcerative colitis（UC） is a kind of inflammatory bowel disease, the etiology is unknown and lack of effective means of prevention and treatment. Our previous studies have shown that Syndecan-1 is a key protein in the pathogenesis of UC and has a protective effect on the intestinal mucosal barrier, but there are few studies on the upstream regulation of Sdc1. LncRNA plays a crucial role in the process of protein transcription and translation, through bioinformatics analysis and prediction, Sdc1 may be the potential target of KIF9-AS1. Moreover, there is a correlation between the two. Therefore, we propose a new intestinal mucosa injury and the pathogenesis mechanism of UC : in response to inflammatory stimuli, KIF9-AS1 transcriptional targeting inhibition of Sdc1 result in damaging of intestinal mucosal barrier function, activating inflammatory cytokines and inflammatory pathways; protective effect of inhibiting the KIF9-AS1/Sdc1 axis may play the prevention and treatment of UC. We will use the inflammation model, over expression and RNA interference methods, as well as the ChIP and dual-luciferase reporter assay and molecular biological methods to explore this hypothesis from in vivo and in vitro, to find a new therapeutic target for disease prevention and provide new intervention methods.