Abstract: FR-PO0178
Tubular TSPO Deficiency Ameliorates Diabetic Kidney Disease by Enhancing Mitochondrial Fatty Acid Oxidation
Session Information
- Diabetic Kidney Disease: Metabolic, Mitochondrial, and Inflammatory Mechanisms
October 23, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Cardiovascular-Kidney-Metabolic Health
- 601 Cardiovascular-Kidney-Metabolic Health: Basic
Authors
- Feng, Yuchen, The University of Hong Kong Li Ka Shing Faculty of Medicine, Hong Kong, Hong Kong
- Yiu, Wai Han, The University of Hong Kong Li Ka Shing Faculty of Medicine, Hong Kong, Hong Kong
- Ma, Jingyuan, The University of Hong Kong Li Ka Shing Faculty of Medicine, Hong Kong, Hong Kong
- Tang, Sydney, The University of Hong Kong Li Ka Shing Faculty of Medicine, Hong Kong, Hong Kong
Background
Mitochondrial dysfunction is a hallmark of diabetic kidney disease (DKD) progression. Our previous study showed that translocator protein (TSPO), located on the mitochondrial outer membrane, was upregulated in renal tubules and involved in regulating energy metabolism and homeostasis in AKI-induced chronic kidney diseases. However, its role in DKD remains elusive.
Methods
TSPO expression was examined in human DKD tissues. Tubule-specific TSPO knockout mice was generated to establish streptozotocin-induced diabetic nephropathy model and db/db mice were treated with antagonist PK11195 for pharmacological inhibition. Proteinuria, renal injury, kidney function, inflammation and fatty acid beta-oxidation pathway were assessed.
Results
TSPO expression was predominantly upregulated in human renal tubules of DKD patients. Genetic deletion of TSPO in renal tubules reduced STZ-induced elevated urine albumin to creatinine (uACR) level, ameliorated renal inflammation and tubulointerstitial injury. Renal function as indicated by serum creatinine and BUN levels were improved compared to wild type diabetic mice. Administration of PK11195 showed protective effects in db/db mice, with reduction in albuminuria, inflammatory cytokine expression and infiltrating immune cells. The renoprotective effect of TSPO blockade was associated with enhanced mitochondrial bioenergetics, as evidenced by increased oxygen consumption rate in tubular cells with TSPO deficiency and elevated expression of fatty acid oxidation-related proteins CPT1 and ACOX1 in both STZ-induced and db/db models.
Conclusion
Upregulation of tubular TSPO contributes to DKD by impairing mitochondrial FAO. Targeting TSPO represents a promising therapeutic intervention for treating diabetic nephropathy.
Acknowledgment
This project is supported by Health and Medical Research Fund (HMRF) of Hong Kong (grant no. 09202356).