Department of Pathophysiology, School of Basic Medical Sciences, Anhui Medical University, Hefei, China.
Department of Gastroenterology, Children's Hospital of Anhui Medical University, Hefei, China.
Helicobacter. 2022 Aug;27(4):e12895. doi: 10.1111/hel.12895. Epub 2022 Apr 19.
Macrophages, as innate immune cells, were reported to participate in the pathogenesis of Helicobacter pylori (H. pylori)-induced gastritis. However, the role and mechanism of macrophage dysfunction in H. pylori-associated pediatric gastritis remain unclear.
An RNA-sequencing assay was used to examine the differential gene expression in normal gastric antrum, non-H. pylori-infected tissue, and H. pylori-infected pediatric gastritis tissue. qPCR assays were applied to verify the expression of target genes. HE staining was performed to identify the occurrence of inflammation in the normal gastric antrum, non-H. pylori-infected tissue, and H. pylori-infected pediatric gastritis tissue. Western blotting was used to measure the expression of SHP2 in pediatric gastritis tissue. The metabolic profile of macrophages was determined via Seahorse metabolic analysis. Flow cytometry analysis was used to examine the level of reactive oxygen species (ROS).
We found that H. pylori -infected gastritis tissue exhibited many differentially expressed genes (DEGs) compared to gastritis tissue without H. pylori infection. Moreover, H. pylori -infected gastritis tissue showed many DEGs annotated with an overactive immune response. We identified that tyrosine-protein phosphatase nonreceptor type 11 (PTPN11), which encodes SHP2, was significantly increased in macrophages of H. pylori -infected gastritis tissue. Furthermore, we revealed that SHP2 could activate the glycolytic function of macrophages to promote H. pylori -induced inflammation. The transcription factor SPI1 , as the downstream molecule of SHP2, could be responsible for the regulation of metabolism-associated gene expression and inflammation.
Our study illustrated the molecular landscape of H. pylori-infected gastritis tissue in children and suggested that the SHP2/SPI1axis could be a novel therapeutic target in H. pylori-induced pediatric gastritis.
巨噬细胞作为先天免疫细胞，据报道参与了幽门螺杆菌（H. pylori）引起的胃炎的发病机制。然而，巨噬细胞功能障碍在 H. pylori 相关小儿胃炎中的作用和机制尚不清楚。
使用 RNA 测序分析来检测正常胃窦、非 H. pylori 感染组织和 H. pylori 感染小儿胃炎组织中的差异基因表达。应用 qPCR 检测来验证靶基因的表达。进行 HE 染色以识别正常胃窦、非 H. pylori 感染组织和 H. pylori 感染小儿胃炎组织中的炎症发生情况。使用 Western blot 测定小儿胃炎组织中 SHP2 的表达。通过 Seahorse 代谢分析来确定巨噬细胞的代谢谱。流式细胞术分析用于检测活性氧（ROS）水平。
我们发现与无 H. pylori 感染的胃炎组织相比，H. pylori 感染的胃炎组织表现出许多差异表达基因（DEGs）。此外，H. pylori 感染的胃炎组织显示出许多注释为过度活跃免疫反应的 DEGs。我们发现，编码 SHP2 的酪氨酸蛋白磷酸酶非受体型 11（PTPN11）在 H. pylori 感染的胃炎组织中的巨噬细胞中显著增加。此外，我们揭示了 SHP2 可以激活巨噬细胞的糖酵解功能，从而促进 H. pylori 诱导的炎症。转录因子 SPI1 作为 SHP2 的下游分子，可能负责调节代谢相关基因表达和炎症。
本研究描绘了儿童 H. pylori 感染性胃炎组织的分子图谱，并表明 SHP2/SPI1 轴可能是 H. pylori 诱导的小儿胃炎的一个新的治疗靶点。
