Bone marrow mesenchymal stem cell-derived CHI3L1 protected against Helicobacter pylori-induced gastric mucosal damage by promoting DNA damage repair via regulating CTCF/CPT1A.

Helicobacter pylori (H. pylori) infection triggers oxidative stress and persistent inflammatory responses, both of which lead to cellular DNA damage while impairing DNA repair. This constitutes a major factor in exacerbating inflammation and subsequently inducing precancerous lesions, with effective interventions still lacking. In our study, we found that bone marrow mesenchymal stem cell-conditioned medium (BMMSC-CM) could alleviate H. pylori-induced DNA damage in gastric mucosal epithelial cells and was further corroborated in vivo studies through immunofluorescence staining and flow cytometry. Screening using solid-phase antibody arrays and transcriptome sequencing revealed that BMMSCs up-regulated CTCF expression in gastric mucosal epithelial cells by secreting the glycoprotein CHI3L1, thereby enhancing Rad51 expression and promoting cellular DNA repair. Meanwhile, untargeted metabolomics and lipidomics further demonstrated that CTCF participated in the DNA repair process through CPT1A-mediated fatty acid oxidation. This study elucidated the role and application value of BMMSC-derived CHI3L1 in treating H. pylori-induced gastric mucosal damage. By exploring the specific mechanism through the regulation of fatty acid oxidation on DNA repair, this study provided new insights and potential therapeutic targets for treating H. pylori infection-related diseases.