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Key modules and differentially expressed genes (DEGs) were recognised in the GSE153224 dataset using weighted gene co\u2010expression network analysis (WGCNA) and examination of differential expression. <jats:italic>IGFBP7<\/jats:italic> was identified as a hub gene by protein\u2013protein interaction (PPI) network and expression validation. CAG patients\u2019 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\u2010methyl\u2010N\u2032\u2010nitro\u2010N\u2010nitrosoguanidine (MNNG) on GES\u20101 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, <jats:italic>IGFBP7<\/jats:italic> was notably underexpressed and selected as a hub gene. ROC analysis confirmed the high diagnostic performance of <jats:italic>IGFBP7<\/jats:italic>. CAG patients treated with VC showed significant improvement in blood parameters and improved gastric mucosal health. In\u00a0vitro, VC increased cell viability, reduced cytotoxicity and apoptosis and lowered COX\u20102 and apoptosis\u2010related protein expression in MNNG\u2010treated GES\u20101 cells. Knockdown of <jats:italic>IGFBP7<\/jats:italic> further influenced these effects. MNNG upregulated HIF\u20101\u03b1\/VEGF signalling proteins, which VC attenuated. Combined VC and <jats:italic>IGFBP7<\/jats:italic> knockdown showed potential protective effects. This study highlights the regulatory role of VC and <jats:italic>IGFBP7<\/jats:italic> in CAG and demonstrates their potential as therapeutic targets for improving gastric mucosal health and mitigating inflammation.<\/jats:p>","DOI":"10.1111\/jcmm.70392","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T02:22:02Z","timestamp":1741746122000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Vitamin C Mediates <scp><i>IGFBP7<\/i><\/scp> to Alleviate Chronic Atrophic Gastritis via the <scp>HIF<\/scp>\u20101\u03b1\/<scp>VEGF<\/scp> Pathway"],"prefix":"10.1111","volume":"29","author":[{"given":"Xun","family":"Cheng","sequence":"first","affiliation":[{"name":"Endoscopy Center, Minhang Hospital Fudan University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hao","family":"Gu","sequence":"additional","affiliation":[{"name":"Endoscopy Center, Minhang 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