Abstract: TH-PO0303
Mechanistic Insights into Mitochondrial Dysfunction in Crb2-Induced Nephrotic Syndrome
Session Information
- Glomerular Diseases: Cell Biology
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology
Authors
- Nomura, Kentaro, Kyorin Daigaku Igakubu Daigakuin Igaku Kenkyuka, Mitaka, Tokyo, Japan
- Yan, Kunimasa, Kyorin Daigaku Igakubu Daigakuin Igaku Kenkyuka, Mitaka, Tokyo, Japan
Background
We previously reported a novel model in which autoantibodies against the transmembrane protein Crb2 on podocyte foot processes induce nephrotic syndrome resembling human minimal change nephrotic syndrome (MCNS) and focal segmental glomerulosclerosis (FSGS) (J Am Soc Nephrol. 33:2008, 2022).
Methods
To investigate the mechanisms of podocyte injury in this model, mice were injected with recombinant mouse Crb2 protein or saline as a control. During the nephrotic phase, isolated glomeruli were analyzed by mass spectrometry and transcriptome analysis. Kidney tissues were examined by light and electron microscopy.
Results
Mass spectrometry and transcriptome analyses consistently demonstrated marked upregulation of molecules involved in mitochondrial energy production in nephrotic glomeruli, regardless of the degree of proteinuria. Light microscopy showed MCNS in mice with moderate proteinuria and FSGS in mice with severe proteinuria. Electron microscopic analysis of glomeruli from controls, MCNS, and unaffected glomerulus with FSGS demonstrated reduced podocyte mitochondrial size in MCNS compared with controls, with a further reduction in FSGS.
Conclusion
A common etiology may underlie both MCNS and FSGS in human, whereas differences in the severity of mitochondrial injury may contribute to their distinct pathological features.