AUF1在TRX1不同表达水平HP感染致胃黏膜病变中作用及机制研究

胃黏膜疾病与幽门螺杆菌(Helicobacter pylori, HP)的关系密切，AUF1作为一种RNA结合蛋白，可以在转录后水平调控基因表达。我们的前期研究发现，HP感染后，AUF1通过结合GKN1 mRNA下调其表达；在胃上皮细胞系中敲减AUF1后，细胞增殖、迁移能力被抑制，S期比例降低；高表达Trx1的HP具有高致病性。本研究将通过干预AUF1表达，在细胞水平检测高低表达Trx1 HP感染后细胞功能、炎症因子、HSP70等的变化，并利用RNA seq方法筛选差异分子，探讨AUF1的下游分子机制；在动物水平，构建AUF1基因敲除小鼠的HP感染模型，检测炎症因子、HSP70的表达水平，并验证差异分子；在临床组织水平分析AUF1与胃黏膜疾病类型、HP感染的相关性及下游分子的表达。本研究旨在明确高Trx1 HP感染后AUF1在胃黏膜致病中的作用及机制，为疾病的早期防治提供理论依据。

Gastric mucosa-related diseases are closely related with helicobacter pylori (HP) infection. AUF1, as an RNA-binding protein, can regulate the expression of genes at post-transcriptional level. Our previous study found that AUF1 downregulated its expression by binding GKN1 mRNA after HP infection. After the AUF1 gene was knockdown in the gastric epithelial cell lines, the cell proliferation and migration were inhibited, and the ratio of s-phase was reduced. HP with high expression of Trx1 is highly pathogenic. In this study, we will further intervene the expression of AUF1, detect the changes in cell function, inflammatory factors and HSP70 expression of gastric epithelial cell lines after high and low Trx1 HP infection at the cell level, and screen differential molecules by RNA seq method to explore the downstream molecular mechanism of AUF1. At the animal level, the HP infection model of AUF1 gene knockout mice was constructed, the expression levels of inflammatory factors and HSP70 were detected, and the differential molecules were verified. The correlation between AUF1 and gastric mucosal disease type, HP infection and the expression level of its downstream molecules were analyzed at the clinical tissue level. The purpose of this study was to clarify the effects and mechanism of AUF1 in gastric mucosa pathological process during HP infection with variable expression levels of Trx1, so as to provide a theoretical basis for the early prevention and treatment of the disease.