VASN/Trx轴在幽门螺杆菌及其毒力因子CagA致病中的作用及机制研究

幽门螺杆菌（Hp）及其毒力因子CagA通过调控细胞增殖与凋亡和介导炎症反应诱发疾病，但该机制尚未完全阐明。我们前期细胞转录组研究和TCGA数据库挖掘分析均发现Hp可诱导VASN和硫氧还蛋白（Trx）高表达。文献报道Hp使VASN上游基因STAT3和HIF-1α表达上调。已知VASN可调节Trx活性，而Trx具有抗凋亡、促增殖、调节免疫和炎症反应等功能。据此我们假设：Hp上调STAT3和HIF-1α表达，二者通过介导VASN/Trx轴调控细胞增殖与凋亡和免疫与炎症反应致病。为此本课题拟研究：①Hp和CagA对STAT3/HIF-1α信号和VASN/Trx轴的影响及与疾病关系；②Hp是否通过STAT3和HIF-1α介导VASN表达；③Hp可否通过VASN/Trx轴调控细胞增殖与凋亡和免疫炎症反应导致疾病。旨在从VASN/Trx轴角度探讨Hp及CagA的作用，为Hp相关性疾病的防治提供新靶点。

Helicobacter pylori (Hp) and its virulence factor CagA induce diseases by regulating cell proliferation and apoptosis and mediating inflammation, but the mechanism has not been fully elucidated. Our previous study in cellular transcriptomics and database mining with TCGA found that Hp could induce high-level expression of Vasorin (VASN) and thioredoxin (Trx). It is reported that Hp can induce the up-regulated expression of STAT3 and HIF-1α in the upstream gene of VASN. VASN is known to regulate activity of Trx, while Trx has functions such as anti-apoptosis, pro-proliferation, regulation of immune and inflammatory responses. Accordingly, we hypothesized that Hp induce the up-regulated expression of STAT3 and HIF-1α, both of which induce disease by mediating the VASN/Trx axis to regulate cell proliferation, apoptosis and immune and inflammatory reactions. Therefore, this project intends to study: (1) The effects of Hp and CagA on STAT3/HIF-1α expression and VASN/Trx axis and their relationship with disease; (2) To verify that Hp can mediate VASN by regulating the expression of STAT3 and HIF-1α; (3) To confirm that Hp can regulate cell proliferation, apoptosis, immune and inflammatory responses through VASN/Trx axis. This study aims to explore the role of Hp and CagA through VASN/Trx axis, and provide new therapeutic targets for the prevention and treatment of Hp-related diseases.