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

Author:

Xu Jiatong12,Li Jiaying3,Li Yan1,Shi Xiaoxiao3,Zhu Huadong1,Chen Limeng3ORCID

Affiliation:

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.

Funder

National High Level Hospital Clinical Research Funding

National Natural Scientific Foundation of China

National Key R&D Program of China

CAMS Innovation Fund for Medical Sciences

Capital’s Funds for Health Improvement and Research

Beijing Natural Science Foundation

Capital Exemplary Research Wards Project

Publisher

MDPI AG

Subject

Molecular Biology,Biochemistry

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