Hp-LPS通过外泌体HDAC6调控STAT3激活自噬通路促进胃粘膜损伤的机制研究

基于前期研究结果，即发现幽门螺杆菌(Hp)脂多糖（LPS）通过MDM2-P63负反馈引起了胃粘膜炎症的发生、发展(Int. J. Cancer. 2015)。近期我们研究发现，Hp-LPS促进巨噬细胞外泌体中HDAC6的释放，上调SOCS3的表达，并激活自噬通路，同时引起胃粘膜细胞恶性转化。进一步机制研究发现，外泌体HDAC6能上调STAT3的表达，结合生物信息学分析STAT3可调控SOCS3的表达。由此我们提出Hp-LPS通过外泌体HDAC6调控STAT3/SOCS3激活自噬通路促进胃粘膜损伤的科学假说。本研究拟用运用CHIP、双荧光素酶报告基因、EMSA、胃类器官等手段，进一步探讨外泌体HDAC6在Hp感染致病中的调控作用及其机制。

Based on the results of previous studies, we found that Helicobacter pylori (Hp) lipopolysaccharide (LPS) caused the occurrence and development of gastric mucosal injury through MDM2-P63 negative feedback. (Int. J. Cancer. 2015). Our recent research has found that that Hp-LPS promoted the release of exosomal-HDAC6 from macrophages, increased the expression of SOCS3 and activated the autophagy pathway and caused malignant transformation of gastric mucosal cells at the same time. Further study found that exosomal-HDAC6 upregulated STAT3. Bioinformatics analysis shows that STAT3 regulates SOCS3 expression as a transcription factor. Thus, we put forward the scientific hypothesis that Hp-LPS promotes gastric mucosal injury by regulating STAT3/SOCS3 to activate autophagy pathway through exosomal-HDAC6. In this study, CHIP, luciferase reporter, EMSA, gastric organoid etc. were used to explore the role of exosomal-HDAC6 in the pathogenesis of Hp infection.