Integrated transcriptomic and proteomic profiling suggests PDK4 and cell cycle-related responses to electroacupuncture in a rat model of chronic atrophic gastritis

Background Chronic atrophic gastritis (CAG) is a precancerous gastric lesion. Although electroacupuncture (EA) can improve CAG-related symptoms and mucosal injury, its molecular responses remain unclear. Methods Male SPF SD rats were assigned to Control, CAG Model, and EA groups. CAG was induced by a multifactorial protocol. EA was applied at Zusanli (ST36) and Zhongwan (CV12) for 20min/day for 2 weeks. Gastric histopathology was evaluated via hematoxylin-eosin staining. To identify candidate targets of EA for CAG, integrated transcriptomics and data-independent acquisition (DIA) proteomics were employed. Subsequent validation was performed by RT-qPCR. Results EA significantly attenuated gastric mucosal atrophy and inflammatory cell infiltration, accompanied by reduced CDK4 and CDK6 mRNA levels ( P < 0.05). Transcriptomics identified 1662 DEGs enriched in estrogen signaling pathway and transcriptional misregulation in cancer signaling pathway. DIA-based proteomic identified 298 DEPs enriched in drug metabolism, amino acid metabolism, muscle contraction, muscle regulation, and mitochondrial metabolism. Integrated analysis identified 24 concordant DEGs/DEPs and RT-qPCR confirmed significant downregulation of PDK4 in the EA group (P<0.01). Conclusion EA ameliorated gastric mucosa injury in CAG rats. Downregulation of PDK4 and CDK4/CDK6 mRNA was associated with EA intervention and may contribute to the amelioration of gastric mucosal injury in CAG.