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

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 diagnosti...

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Main Authors: Jiatong Xu, Jiaying Li, Yan Li, Xiaoxiao Shi, Huadong Zhu, Limeng Chen
Format: Article
Language:English
Published: MDPI AG 2023-08-01
Series:Biomolecules
Subjects:
Online Access:https://www.mdpi.com/2218-273X/13/9/1329
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author Jiatong Xu
Jiaying Li
Yan Li
Xiaoxiao Shi
Huadong Zhu
Limeng Chen
author_facet Jiatong Xu
Jiaying Li
Yan Li
Xiaoxiao Shi
Huadong Zhu
Limeng Chen
author_sort Jiatong Xu
collection DOAJ
description 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.
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spelling doaj.art-6840dd90dd8a487b86e1dfefabc65cd82023-11-19T09:45:28ZengMDPI AGBiomolecules2218-273X2023-08-01139132910.3390/biom13091329Multidimensional Landscape of SA-AKI Revealed by Integrated Proteomics and Metabolomics AnalysisJiatong Xu0Jiaying Li1Yan Li2Xiaoxiao Shi3Huadong Zhu4Limeng Chen5Emergency 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, ChinaDepartment 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, ChinaEmergency 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, ChinaDepartment 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, ChinaEmergency 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, ChinaDepartment 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, ChinaSepsis-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.https://www.mdpi.com/2218-273X/13/9/1329SA-AKIproteomicsmetabolomicsbiomarkermitochondrial dysfunction
spellingShingle Jiatong Xu
Jiaying Li
Yan Li
Xiaoxiao Shi
Huadong Zhu
Limeng Chen
Multidimensional Landscape of SA-AKI Revealed by Integrated Proteomics and Metabolomics Analysis
Biomolecules
SA-AKI
proteomics
metabolomics
biomarker
mitochondrial dysfunction
title Multidimensional Landscape of SA-AKI Revealed by Integrated Proteomics and Metabolomics Analysis
title_full Multidimensional Landscape of SA-AKI Revealed by Integrated Proteomics and Metabolomics Analysis
title_fullStr Multidimensional Landscape of SA-AKI Revealed by Integrated Proteomics and Metabolomics Analysis
title_full_unstemmed Multidimensional Landscape of SA-AKI Revealed by Integrated Proteomics and Metabolomics Analysis
title_short Multidimensional Landscape of SA-AKI Revealed by Integrated Proteomics and Metabolomics Analysis
title_sort multidimensional landscape of sa aki revealed by integrated proteomics and metabolomics analysis
topic SA-AKI
proteomics
metabolomics
biomarker
mitochondrial dysfunction
url https://www.mdpi.com/2218-273X/13/9/1329
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