Abstract: FR-PO171
Proteomics and Metabolomics Conjoint Analysis Revealed Mitochondrial Function and Metabolic Disorders in Sepsis-Induced AKI
Session Information
- AKI: Mechanisms - II
November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Xu, Jiatong, Peking Union Medical College Hospital, Dongcheng-qu, Beijing, China
- Shi, Xiaoxiao, Peking Union Medical College Hospital, Dongcheng-qu, Beijing, China
- Li, Jiaying, Peking Union Medical College Hospital, Dongcheng-qu, Beijing, China
- Li, Yan, Peking Union Medical College Hospital, Dongcheng-qu, Beijing, China
- Zhu, Huadong, Peking Union Medical College Hospital, Dongcheng-qu, Beijing, China
- Chen, Limeng, Peking Union Medical College Hospital, Dongcheng-qu, Beijing, China
Background
Sepsis-induced acute kidney injury (S-AKI) is a severe and life-threatening condition with high morbidity and mortality and poses a significant risk of chronic kidney disease. However, the early diagnosis and precaution of S-AKI remain challenged due to lacking effective diagnostic biomarkers and treatment targets.
Methods
We established an S-AKI mouse model using intraperitoneal injection of lipopolysaccharide (LPS) and control mice with 0.9% saline (both n=5). After 24 hours, the mice were euthanized to collect blood and kidney samples. The kidney proteins and dissolved metabolites were analyzed using liquid chromatography-tandem mass spectrometry. We integrated proteomics and metabolomics analysis approaches through various bioinformatic analyses, including Gene Set Enrichment Analysis (GSEA), protein and protein interactions (PPI), and MetaboAnalyst analysis.
Results
A total of 5185 proteins were identified in the kidney, including 353 upregulated and 166 downregulated proteins in S-AKI mice compared with the control group. The GO and KEGG analysis of the differentially expressed proteins (DEPs) indicated that downregulated proteins in S-AKI kidneys were primarily involved in mitochondrial functions such as mitochondrial translation and mitochondrial respiratory chain complex assembly. The hub proteins in PPI networks were mainly involved in the mitochondrial electron transport chain. The GSEA also indicated that mitochondrial dysfunction was an incredibly crucial facilitator for S-AKI development. S-AKI kidneys had 111 increased and 66 decreased metabolites compared to the control group. MetaboAnalyst enrichment analysis suggested that S-AKI mainly caused disorders of central carbon metabolism (such as transfer of acetyl groups into mitochondria, Warburg effect, and citric acid cycle), amino acid metabolism, and nicotinate and nicotinamide metabolism.
Conclusion
Proteomics and Metabolomics conjoint analysis provides new insights and a more comprehensive understanding of the pathophysiology of S-AKI with mitochondrial function and metabolic disorders, contributing to new diagnostic biomarkers and therapeutic targets.