Abstract: SA-PO0651
Metabolic Reprogramming Characterizes Renal Tubular Epithelial Cells in Bardet-Biedl Syndrome
Session Information
- Monogenic Kidney Diseases: Tubular and Other
November 08, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1201 Genetic Diseases of the Kidneys: Monogenic Kidney Diseases
Authors
- Capasso, Giovambattista, Biogem, Biology and Molecular Genetics Institute, Ariano Irpino, Italy
- Villanova, Antonio, Biogem, Biology and Molecular Genetics Institute, Ariano Irpino, Italy
- Shafqat, Almera, Biogem, Biology and Molecular Genetics Institute, Ariano Irpino, Italy
- D'Agostino, Giulia, Biogem, Biology and Molecular Genetics Institute, Ariano Irpino, Italy
- Iannaccone, Antonella, Biogem, Biology and Molecular Genetics Institute, Ariano Irpino, Italy
- Suzumoto, Yoko, Biogem, Biology and Molecular Genetics Institute, Ariano Irpino, Italy
- Zacchia, Miriam, Department of Translational Medical Sciences, University of Campania ‘Luigi Vanvitelli’, Naples, Italy
Background
Fibrosis is the final common pathway of almost all types of repetitive kidney injury and is considered as a hallmark of chronic kidney diseases (CKD). Multiple lines of evidence suggest that renal epithelial metabolic abnormalities directly contribute to fibrosis development in several models of CKD. The present study has investigated the urine metabolite signature and cellular bioenergetics in Bardet-Biedl syndrome (BBS), a rare kidney ciliopathy.
Methods
Untargeted metabolomics of urine samples from 30 BBS patients and 32 controls was carried out. Disturbance in glycolysis, lipid and mitochondrial homeostasis were investigated in vitro utilizing mouse inner medullar collecting duct cell line lacking Bbs10 (IMCD3-Bbs10-/- cells) and wildtype.
Results
Urine metabolomic fingerprinting of BBS patients differed from controls, demonstrating an increased urinary excretion of several monocarboxylates, including lactic acid (LA), in the absence of increased circulating levels. In addition, IMCD3-Bbs10-/- cells displayed a) increased mRNA and protein abundances of major enzymes involved in aerobic glycolysis such as Glucose Transporter 1 (Glut1) and Hexokinase 1 (HK1); b) increased intracellular lipid accumulation; c) signs of mitochondrial dysfunction. In particular, dysregulation of Pink-Parkin signalling pathway, as demonstrated by reduced Pink1 and Parkin abundances, may indicate the altered mitochondrial quality control and mitophagy. Moreover, IMCD3-Bbs10-/- cells showed significantly increased α-SMA protein expression, indicating epithelial-mesenchymal transition (Fig.1).
Conclusion
This study highlights the presence of metabolic and mitochondrial abnormalities in renal epithelial cells in a model of BBS. The disrupted Pink-Parkin signaling pathway pointed out the abnormal mitochondrial quality control, a key factor in cellular stress responses and kidney pathology. Further investigations are required to elucidate the molecular mechanisms and role of these deregulations in CKD progression in BBS.
Funding
- Government Support – Non-U.S.