Study on the Mechanism of UMI-77 in the Treatment of Sepsis-Induced Acute Lung Injury Based on Transcriptomics and Metabolomics
Jiatian Zhang,1,* Zhelin Xia,2,* Cuicui Dong,3 Jiaqi Zhu,3 Hang Ni,1 Yubin Xu,2,* Yinghe Xu4,* 1Department of Critical Care Medicine, Taizhou Hospital of Zhejiang Province, Shaoxing University, Shaoxing, 312000, People’s Republic of China; 2Department of Pharmacy, Tai...
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Dove Medical Press
2024-12-01
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| Series: | Journal of Inflammation Research |
| Subjects: | |
| Online Access: | https://www.dovepress.com/study-on-the-mechanism-of-umi-77-in-the-treatment-of-sepsis-induced-ac-peer-reviewed-fulltext-article-JIR |
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| Summary: | Jiatian Zhang,1,* Zhelin Xia,2,* Cuicui Dong,3 Jiaqi Zhu,3 Hang Ni,1 Yubin Xu,2,* Yinghe Xu4,* 1Department of Critical Care Medicine, Taizhou Hospital of Zhejiang Province, Shaoxing University, Shaoxing, 312000, People’s Republic of China; 2Department of Pharmacy, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, 318000, People’s Republic of China; 3Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, 317000, People’s Republic of China; 4Department of Critical Care Medicine, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, 317000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yubin Xu, Department of Pharmacy, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, 318000, People’s Republic of China, Email xuyubin1988@126.com Yinghe Xu, Department of Critical Care Medicine, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, 317000, People’s Republic of China, Email xuyh@tzc.edu.cnIntroduction: 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.Keywords: sepsis-induced ALI, inflammation, genes, metabolites, cytokine signaling |
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| ISSN: | 1178-7031 |