Multidimensional Landscape of SA-AKI Revealed by Integrated Proteomics and Metabolomics Analysis

Jiatong Xu; Jiaying Li; Yan Li; Xiaoxiao Shi; Huadong Zhu; Limeng Chen

doi:10.3390/biom13091329

Multidimensional Landscape of SA-AKI Revealed by Integrated Proteomics and Metabolomics Analysis

Biomolecules. 2023 Aug 30;13(9):1329. doi: 10.3390/biom13091329.

Authors

Jiatong Xu^{1

2}, Jiaying Li³, Yan Li¹, Xiaoxiao Shi³, Huadong Zhu¹, Limeng Chen³

Affiliations

¹ Emergency Department, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, China.
² Medical Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, China.
³ Department of Nephrology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, China.

Abstract

Sepsis-associated acute kidney injury (SA-AKI) is a severe and life-threatening condition with high morbidity and mortality among emergency patients, and it poses a significant risk of chronic renal failure. Clinical treatments for SA-AKI remain reactive and non-specific, lacking effective diagnostic biomarkers or treatment targets. In this study, we established an SA-AKI mouse model using lipopolysaccharide (LPS) and performed proteomics and metabolomics analyses. A variety of bioinformatic analyses, including gene set enrichment analysis (GSEA), weighted gene co-expression network analysis (WGCNA), protein and protein interactions (PPI), and MetaboAnalyst analysis, were conducted to investigate the key molecules of SA-AKI. Integrated proteomics and metabolomics analysis revealed that sepsis led to impaired renal mitochondrial function and metabolic disorders. Immune-related pathways were found to be activated in kidneys upon septic infection. The catabolic products of polyamines accumulated in septic kidneys. Overall, our integrated analysis provides a multidimensional understanding of SA-AKI and identifies potential pathways for this condition.

Keywords: SA-AKI; biomarker; metabolomics; mitochondrial dysfunction; proteomics.

Grants and funding

This research was funded by National High Level Hospital Clinical Research Funding (2022-PUMCH-B-109, 2022-PUMCH-D-005, 2022-PUMCH-B-019, 2022-PUMCH-D-002), National Natural Scientific Foundation of China (82170709, 81970607), the National Key R&D Program of China (2022ZD0116003), CAMS Innovation Fund for Medical Sciences (CIFMS 2021-I2M-1-003), Capital’s Funds for Health Improvement and Research (CFH 2020-2-4018), Beijing Natural Science Foundation (L202035), and the Capital Exemplary Research Wards Project (BCRW202001).