Vitamin C Mediates IGFBP7 to Alleviate Chronic Atrophic Gastritis via the HIF-1α/VEGF Pathway.

Chronic atrophic gastritis (CAG) is a precancerous lesion characterised by gastric mucosal atrophy and inflammation. Identifying key molecular mechanisms and potential therapeutic targets is essential to improve patient outcomes. Key modules and differentially expressed genes (DEGs) were recognised in the GSE153224 dataset using weighted gene co-expression network analysis (WGCNA) and examination of differential expression. IGFBP7 was identified as a hub gene by protein-protein interaction (PPI) network and expression validation. CAG patients' blood parameters and gastric mucosal health status were evaluated before and after the treatment of vitamin C (VC). In addition, we investigated the effects of VC and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) on GES-1 cells, including cell viability, apoptosis and the expression of inflammatory and angiogenic markers. WGCNA identified that the blue module was significantly associated with CAG with a correlation coefficient 0.924. Among 93 overlapping genes, IGFBP7 was notably underexpressed and selected as a hub gene. ROC analysis confirmed the high diagnostic performance of IGFBP7. CAG patients treated with VC showed significant improvement in blood parameters and improved gastric mucosal health. In vitro, VC increased cell viability, reduced cytotoxicity and apoptosis and lowered COX-2 and apoptosis-related protein expression in MNNG-treated GES-1 cells. Knockdown of IGFBP7 further influenced these effects. MNNG upregulated HIF-1α/VEGF signalling proteins, which VC attenuated. Combined VC and IGFBP7 knockdown showed potential protective effects. This study highlights the regulatory role of VC and IGFBP7 in CAG and demonstrates their potential as therapeutic targets for improving gastric mucosal health and mitigating inflammation.