SHP2/SPI1axis promotes glycolysis and the inflammatory response of macrophages in Helicobacter pylori‐induced pediatric gastritis

Abstract

Background 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. Materials and Methods 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). Results 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. Conclusion 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.

Mitochondrial dysfunction induced by HIF‐1α under hypoxia contributes to the development of gastric mucosal lesions

“…Glycolysis is an important metabolic pathway controlled by many glycolytic enzymes, and previous reports have confirmed that gastric mucosal diseases utilise glycolysis to meet energy demands. [41][42][43] Based on a transcriptional sequencing assay of clinical PHT-induced injured gastric mucosal tissues combined with energy metabolism analysis of primary gastric mucosal epithelial cells from PHT model mice, we found that glycolysis was activated and regulated by the key rate-limiting enzyme LDHA in the gastric mucosa of PHT models under hypoxia. Elevated glycolysis and LDHA were also measured in GC cells and gastric mucosal tissues with cancerous lesions under hypoxic condition.…”

Targeting hexokinase 1 alleviates NLRP3‐mediated inflammation in apical periodontitis: A laboratory investigation

“…Recent studies have suggested that the activation of a glycolytic phenotype is linked to immune responses (Song et al, 2022; Wang, Yu et al, 2022). During the peak of inflammation, immune cells preferentially use glycolysis as their primary source of energy (Li, Lu et al, 2022). Glycolysis is an effective method of rapid access to ATP, and the production of ATP by glycolysis is about 100 times faster than oxidative phosphorylation, in order to meet the sudden increased energy demands (Vander Heiden et al, 2009).…”