Dataset Information

Data-Independent Acquisitions Uncover Kidney Proteome Remodeling during Ischemic Reperfusion Kidney Injury using a Fast-scanning ZenoTOF 7600

ABSTRACT: Acute kidney injury (AKI) manifests as a major health concern particularly for the elderly and understanding related proteome changes is critical for prevention and development of novel therapeutics to recover kidney function, and to mitigate the susceptibility for recurrent AKI, or development of chronic kidney disease. In this study, mouse kidneys were subjected to ischemia-reperfusion injury while the contralateral kidneys remained uninjured to assess changes in the kidney proteome. A fast-scanning ZenoTOF 7600 mass spectrometer was used for comprehensive data-independent acquisition (DIA) for protein identification and quantification. Short microflow gradients, and the generation of a deep kidney-specific spectral library allowed for comprehensive and high-throughput assays. Upon AKI the kidney proteome was completely remodeled, and over half of the 3,945 quantified protein groups changed significantly. Downregulated proteins in the injured kidney were involved in energy production, including numerous peroxisomal matrix proteins, many related to lipid metabolism, such as ACOX1, CAT, EHHADH, ACOT4, ACOT8, and Scp2. Injured mice exhibited severely declined health. The comprehensive and sensitive kidney-specific DIA assays, highlighted in this work, feature high-throughput analytical capabilities to achieve deep coverage of the kidney proteome, and will serve as useful tool for the development of novel therapeutics aimed at remediating kidney function.

INSTRUMENT(S): ZenoTOF 7600

ORGANISM(S): Mus Musculus (ncbitaxon:10090)

SUBMITTER: Birgit Schilling

PROVIDER: MSV000090777 | MassIVE | Wed Nov 23 11:51:00 GMT 2022

SECONDARY ACCESSION(S): PXD038339

REPOSITORIES: MassIVE

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Publications

Substantial downregulation of mitochondrial and peroxisomal proteins during acute kidney injury revealed by data-independent acquisition proteomics.

Burton Jordan B JB Silva-Barbosa Anne A Bons Joanna J Rose Jacob J Pfister Katherine K Simona Fabia F Gandhi Tejas T Reiter Lukas L Bernhardt Oliver O Hunter Christie L CL Goetzman Eric S ES Sims-Lucas Sunder S Schilling Birgit B

Proteomics 20230929 5

Acute kidney injury (AKI) manifests as a major health concern, particularly for the elderly. Understanding AKI-related proteome changes is critical for prevention and development of novel therapeutics to recover kidney function and to mitigate the susceptibility for recurrent AKI or development of chronic kidney disease. In this study, mouse kidneys were subjected to ischemia-reperfusion injury, and the contralateral kidneys remained uninjured to enable comparison and assess injury-induced chang ...[more]

PMID: 37775337

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Project description:Microarray analysis of human kidneys with acute kidney injury (AKI) has been limited because such kidneys are seldom biopsied. However, all kidney transplants experience AKI, and early kidney transplants without rejection are an excellent model for human AKI: they are screened to exclude chronic kidney disease, frequently biopsied, and have extensive follow-up. We used histopathology and microarrays to compare indication biopsies from 28 transplants with AKI to 11 pristine protocol biopsies of stable transplants. Kidneys with AKI showed increased expression of 394 injury-repair response associated transcripts, including many known epithelial injury molecules (e.g. ITGB6, LCN2), tissue remodeling molecules (e.g. VCAN), and inflammation molecules (S100A8, ITGB3). Many other genes also predict the phenotype, depending on statistical filtering rules, including AKI biomarkers as HAVCR1 and IL18. Most mouse orthologs of the top injury-repair transcripts were increased in published mouse AKI models. Pathway analysis of the injury-repair transcripts revealed similarities to cancer, development, and cell movement. The injury-repair transcript score AKI kidneys correlated with reduced function, future recovery, brain death, and need for dialysis, but not future graft loss. In contrast, histologic features of "acute tubular injury" did not correlate with function or with the molecular changes. Thus the injury-repair associated transcripts represent a massive coordinate injury-repair response of kidney parenchyma to AKI, similar to mouse AKI models, and provide an objective measure for assessing the severity of AKI in kidney biopsies and validation for the use of many AKI biomarkers. AKI biopsies sample names and CEL files are from GSE21374. All consenting renal transplant patients undergoing biopsies for cause as standard of care between 09/2004 and 10/2007 at the university of Alberta or between 11/2006 and 02/2007 at the University of Illinois were included in the analysis. In addition to the cores required for standard histopathology, we collected one core for gene expression studies. the relationship between gene expression in the biopsy and subsequent graft loss was analyzed. This dataset is part of the TransQST collection.

Dataset Information

Data-Independent Acquisitions Uncover Kidney Proteome Remodeling during Ischemic Reperfusion Kidney Injury using a Fast-scanning ZenoTOF 7600

Publications

Substantial downregulation of mitochondrial and peroxisomal proteins during acute kidney injury revealed by data-independent acquisition proteomics.

Similar Datasets

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