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Study on the Mechanism of UMI-77 in the Treatment of Sepsis-Induced Acute Lung Injury Based on Transcriptomics and
Jiatian Zhang1, Zhelin Xia2, Cuicui Dong3
1Department of Critical Care Medicine, Taizhou Hospital of Zhejiang Province, Shaoxing University, Shaoxing, 312000, People's Republic of China.
Introduction:
Sepsis-induced acute lung injury (ALI), a critical sequela of systemic inflammation, often progresses to acute respiratory distress syndrome, conferring high mortality. Although UMI-77 has demonstrated efficacy in mitigating lung injury in sepsis, the molecular mechanisms underlying its action have not yet been fully elucidated.
Methods:
This study aimed to delineate the mechanism by which UMI-77 counteracts sepsis-induced ALI using comprehensive transcriptomic and metabolomic analyses.
Results:
UMI-77 significantly ameliorated histopathological changes in the lungs of mice with sepsis-induced ALI Transcriptomic analysis revealed that 124 differentially expressed genes were modulated by UMI-77 and were predominantly implicated in chemokine-mediated signaling pathways, apoptosis regulation, and inflammatory responses. Integrated metabolomic analysis identified Atp4a, Ido1, Ctla4, and Cxcl10 as key genes, and inosine 5'-monophosphate (IMP), thiamine monophosphate, thymidine 3',5'-cyclic monophosphate (dTMP) as key differential metabolites. UMI-77 may regulate key genes (Atp4a, Ido1, Ctla4, and Cxcl10) to affect key metabolites (IMP, thiamine monophosphate, and dTMP) and their target genes (Entpd2, Entpd1, Nt5e, and Hprt) involved in cytokine-cytokine receptor interaction, gastric acid secretion, pyrimidine, and purine metabolism in the treatment of sepsis-induced ALI.
Conclusion:
UMI-77 exerts its therapeutic effect in sepsis-induced ALI through intricate modulation of pivotal genes and metabolites, thereby influencing critical biological pathways. This study lays the groundwork for further development and clinical translation of UMI-77 as a potential therapeutic agent for sepsis-associated lung injuries.
