Abstract: FR-PO0180
HNF4α Alleviates Diabetic Kidney Disease by BNIP3-Mediated Mitochondrial Homeostasis
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
- Lu, Hao, The University of Hong Kong Li Ka Shing Faculty of Medicine, Hong Kong, Hong Kong
- Chen, Hai-Yong, The University of Hong Kong Li Ka Shing Faculty of Medicine, Hong Kong, Hong Kong
Background
Hepatic nuclear factor 4α (HNF4α) is a transcription factor that plays vital role in embryonic development and metabolism. However, its role in diabetic kidney disease (DKD) remains unknown. This study aims to elucidate the underlying mechanism by which HNF4α maintains mitochondrial homeostasis in renal tubular cells and attenuates the progression of DKD.
Methods
We examined the expression of HNF4α, BNIP3 and ANXA5, along with renal function parameters in db/db mice. Additionally, the gain- and loss- function of HNF4α and downstream proteins in high glucose-treated tubular epithelial cells were employed. Mitochondrial homeostasis was assessed by measuring mitochondrial membrane potential (MMP), reactive oxygen species (ROS) levels, ATP production and mitophagy activity.
Results
HNF4α levels were significantly reduced in the diabetic kidney, correlating with remarkable mitochondrial damage and dysfunction. In vitro, overexpression of HNF4α significantly enhanced mitophagy, stabilized MMP and increased ATP production, and decreased ROS accumulation, accompanied by the upregulation of BNIP3 and ANXA5. Conversely, silencing BNIP3 or ANXA5 partially attenuated HNF-4α mediated mitochondrial protective effects.
Conclusion
The HNF4α/BNIP3/ANXA5 plays critical role in maintaining mitochondrial hemostasis in renal tubular cells during DKD, offering potential therapeutic targets for intervention.
Acknowledgment
This study was supported by grants from the Hong Kong Research Grants Council (17125323, 17125524, and 17125925), and the HKU Seed Funds (2402101703).
Funding
- Government Support – Non-U.S.