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

作者：Xun Cheng, Hao Gu, Yulin Chong, Fan Li, Songhua Bei, Huanqing Li, Jun Jiang, Ming Pan, Li Feng, Xiaohong Zhang · 发表于：Journal of Cellular and Molecular Medicine · 年份：2025 · DOI：10.1111/jcmm.70392 · 被引用次数：4 · 研究领域：Intestinal and Peritoneal Adhesions、Helicobacter pylori-related gastroenterology studies、Intraperitoneal and Appendiceal Malignancies

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/V...