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Updated: Aug 5, 2026
06:23
Modeling Hypoxia/Reoxygenation Injury in Proximal Tubular Epithelial Cells
Published on: November 21, 2025
Impaired Metabolic Remodeling Characterizes Injured Niches during Post-ischemic Kidney Repair
Rosalie G J Rietjens1,2, Benedetta Manzato2,3, Yuheng Liao1
1Department of Internal Medicine (Nephrology) & Einthoven Laboratory of Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, The Netherlands.
Journal of the American Society of Nephrology : JASN
|August 3, 2026
Summary
Kidney injury causes metabolic defects in seemingly healthy cells, hindering regeneration. Spatial omics revealed these abnormalities extend beyond damaged cells, impacting the tissue microenvironment in chronic kidney disease progression.
Area of Science:
- Nephrology
- Metabolomics
- Systems Biology
Background:
- The transition from acute kidney injury to chronic kidney disease is poorly understood.
- The spatial metabolic architecture of injured kidney tissue and its impact on regeneration are not fully characterized.
Purpose of the Study:
- To investigate the spatial metabolic microenvironment of injured kidney tissue.
- To understand how metabolic alterations affect kidney regeneration after injury.
Main Methods:
- Utilized multimodal spatial omics on mouse kidneys post-ischemia-reperfusion injury.
- Employed mass spectrometry imaging (MSI) and spatial transcriptomics (Stereo-seq).
- Integrated metabolomic and transcriptomic data using unsupervised spatial domain analysis and niche projection.
Main Results:
- Identified distinct healthy and injured kidney niches based on lipidome profiles.
- Observed metabolic abnormalities, including altered succinic acid and linoleic acid levels, in proximal tubule cells within injured niches.
- Confirmed transcriptional downregulation of oxidative phosphorylation and fatty acid β-oxidation in these cells.
Conclusions:
- Spatially resolved analysis revealed distinct healthy and injured tissue niches after ischemia-reperfusion injury.
- Metabolic abnormalities are not confined to damaged cells but extend to seemingly healthy cells in injured microenvironments.
- These widespread metabolic defects may impede kidney regeneration and contribute to chronic kidney disease progression.
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