Study on the Mechanism of UMI-77 in the Treatment of Sepsis-Induced Acute Lung Injury Based on Transcriptomics and Metabolomics

Introduction:
Sepsis-induced acute lung injury (ALI), a severe consequence of systemic inflammation, frequently progresses to acute respiratory distress syndrome (ARDS), carrying a high mortality rate. While UMI-77 has shown promise in alleviating lung injury caused by sepsis, its precise molecular mechanisms remain incompletely understood.
Methods:
This study sought to elucidate the mechanisms by which UMI-77 mitigates sepsis-induced ALI, employing integrated transcriptomic and metabolomic analyses.
Results:
UMI-77 markedly improved lung histopathology in mice with sepsis-induced ALI. Transcriptomic profiling identified 124 differentially expressed genes modulated by UMI-77, primarily associated with chemokine signaling, apoptosis regulation, and inflammatory pathways. Metabolomic integration highlighted Atp4a, Ido1, Ctla4, and Cxcl10 as key genes, along with inosine 5′-monophosphate (IMP), thiamine monophosphate, and thymidine 3′,5′-cyclic monophosphate (dTMP) as significant metabolites. UMI-77 appears to influence these genes and metabolites, as well as their downstream targets (Entpd2, Entpd1, Nt5e, and Hprt), modulating pathways involved in cytokine-receptor interactions, gastric acid secretion, and purine and pyrimidine metabolism in the context of sepsis-induced ALI.
Conclusion:
UMI-77 mediates its protective effects in sepsis-induced ALI by orchestrating complex gene-metabolite interactions that regulate critical biological processes. These findings provide a foundation for advancing UMI-77 toward clinical application as a therapeutic strategy for sepsis-related lung injury.