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Updated: Jul 13, 2025
Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice
Published on: May 2, 2025
Untargeted metabolomics analysis on kidney tissues from mice reveals potential hypoxia biomarkers
Muhammad Imran Sajid1,2, Francisco J Nunez1, Farideh Amirrad1
1Department of Biomedical and Pharmaceutical Sciences, Chapman University, 9401 Jeronimo Road, Irvine, CA, 92618-1908, USA.
Abstract:
Chronic hypoxia may have a huge impact on the cardiovascular and renal systems. Advancements in microscopy, metabolomics, and bioinformatics provide opportunities to identify new biomarkers. In this study, we aimed at elucidating the metabolic alterations in kidney tissues induced by chronic hypoxia using untargeted metabolomic analyses. Reverse phase ultrahigh performance liquid chromatography-mass spectroscopy/mass spectroscopy (RP-UPLC-MS/MS) and hydrophilic interaction liquid chromatography (HILIC)-UPLC-MS/MS methods with positive and negative ion mode electrospray ionization were used for metabolic profiling. The metabolomic profiling revealed an increase in metabolites related to carnitine synthesis and purine metabolism. Additionally, there was a notable increase in bilirubin. Heme, N-acetyl-L-aspartic acid, thyroxine, and 3-beta-Hydroxy-5-cholestenoate were found to be significantly downregulated. 3-beta-Hydroxy-5-cholestenoate was downregulated more significantly in male than female kidneys. Trichome Staining also showed remarkable kidney fibrosis in mice subjected to chronic hypoxia. Our study offers potential intracellular metabolite signatures for hypoxic kidneys.
Insights
Chronic hypoxia significantly alters kidney metabolism, increasing carnitine and purine pathways while decreasing key metabolites. This study identifies potential metabolic biomarkers for hypoxic kidney disease.
Area of Science:
- Biochemistry
- Renal Physiology
- Metabolomics
Background:
- Chronic hypoxia poses significant risks to cardiovascular and renal systems.
- Identifying novel biomarkers is crucial for understanding hypoxic injury.
- Metabolomics offers advanced tools for biomarker discovery.
Purpose of the Study:
- To investigate metabolic changes in kidney tissues under chronic hypoxia.
- To identify potential intracellular metabolite signatures associated with hypoxic kidneys.
Main Methods:
- Untargeted metabolomic analysis using RP-UPLC-MS/MS and HILIC-UPLC-MS/MS.
- Positive and negative ion mode electrospray ionization for comprehensive profiling.
- Trichome Staining to assess kidney fibrosis.
Main Results:
- Increased metabolites involved in carnitine synthesis and purine metabolism.
- Elevated levels of bilirubin observed.
- Significant downregulation of heme, N-acetyl-L-aspartic acid, thyroxine, and 3-beta-Hydroxy-5-cholestenoate.
- Sex-specific downregulation of 3-beta-Hydroxy-5-cholestenoate in male kidneys.
- Evidence of kidney fibrosis in hypoxic mice.
Conclusions:
- Chronic hypoxia induces distinct metabolic alterations in the kidney.
- Identified metabolites may serve as biomarkers for hypoxic kidney conditions.
- Findings highlight potential sex differences in hypoxic kidney injury response.
