Abstract
BackgroundChronic atrophic gastritis (CAG) is a chronic disease of the gastric mucosa characterized by a reduction or an absolute disappearance of the original gastric glands, possibly replaced by pseudopyloric fibrosis, intestinal metaplasia, or fibrosis. CAG develops progressively into intestinal epithelial metaplasia, dysplasia, and ultimately, gastric cancer. Epidemiological statistics have revealed a positive correlation between the incidence of CAG and age. Mesenchymal stem cells (MSCs) are a type of adult stem cells derived from mesoderm, with strong tissue repair capabilities. Therefore, the restoration of the gastric mucosa may serve as an efficacious strategy to ameliorate CAG and avert gastric cancer. However, the mechanisms by which MSCs inhibit the relentless progression of aging atrophic gastritis remain to be elucidated. This study endeavored to assess a novel approach utilizing MSCs to treat CAG and forestall carcinogenics.MethodsIn this study, we selected mice with atrophic gastritis from naturally aging mice and administered human umbilical cord-derived mesenchymal stem cells (hUMSCs) via tail vein injection to evaluate the therapeutic effects of hUMSCs on age-related chronic atrophic gastritis. Initially, we employed methods such as ELISA, immunohistochemical analysis, and TUNEL assays to detect changes in the mice post-hUMSC injection. Proteomic and bioinformatics analyses were conducted to identify differentially expressed proteins, focusing on NADH: ubiquinone oxidoreductase core subunit S8 (Ndufs8). Co-culturing hUMSCs with Ndufs8 knockout gastric mucosal epithelial cells (GMECs), we utilized flow cytometry, Western blotting, real-time quantitative PCR, and immunofluorescence to investigate the mechanisms of action of hUMSCs.ResultsWe observed that hUMSCs are capable of migrating to and repairing damaged gastric mucosa. Initially, hUMSCs significantly enhanced the secretion of gastric proteins PG-1 and G17, while concurrently reducing inflammatory cytokines. Furthermore, hUMSCs mitigated gastric fibrosis and apoptosis in mucosal cells. Proteomic and bioinformatic analyses revealed alterations in the protein network involved in mitochondrial autophagy, with Ndufs8 playing a pivotal role. Upon knocking out Ndufs8 in GMECs, we noted mitochondrial damage and reduced autophagy, leading to an aged phenotype in GMECs. Co-culturing Ndufs8-knockout GMECs with hUMSCs demonstrated that hUMSCs could ameliorate mitochondrial dysfunction and restore the cell cycle in GMECs.
Published Version
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