Abstract: TH-PO945
Role of Podocyte Ceramide Synthase 6 and C16 Ceramide in Aging-Related Kidney Changes in Marmosets
Session Information
- Geriatric Nephrology: Innovations and Insights
October 24, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Geriatric Nephrology
- 1300 Geriatric Nephrology
Authors
- Yuan, Yihan, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
- Wang, Qinyue, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
- Zhao, Qingwei, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
- Lee, Hak Joo, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
- Tamayo, Ian M., The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
- Trevino, Esmeralda, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
- Kasinath, Balakuntalam S., The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
- Zhou, Daohong, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
- Sharma, Kumar, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
- Zhang, Guanshi, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
Background
The marmoset, a nonhuman primate, has been established as a valuable model for studying the aging kidney. Aged marmosets’ kidneys exhibit glomerulosclerosis, tubular fibrosis, and an increased urinary albumin to creatinine ratio. Signaling pathways related to protein synthesis and fibrosis were activated in the kidneys of these aged marmosets. Matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) analysis has revealed alterations in lipid profiles within the glomeruli of aging mouse kidneys, with a particular accumulation of ceramides (Cer) in the aging kidney. However, the role of Cer metabolism in the progression of aging-related renal changes in marmosets remains unclear.
Methods
We investigated the lipid profile in glomeruli in situ using MALDI-MSI-based spatial metabolomics (spatial resolution: 20 μm). The study included young male and female (around 3 years; n=4/gender), aged male and female (around 16 years; n=5/gender) marmosets from the Southwest National Primate Research Center. A targeted list of lipids involved in ceramide metabolism was extracted from the glomeruli of young and aged marmosets for comparisons. The protein level of Cer synthase 6 (CERS6) in kidney cortical tissues was measured using western blotting. Given that CERS6 is specifically expressed in podocytes of human kidneys according to single-cell transcriptomics, immunofluorescence (IF) staining was employed using anti-synaptopodin (a podocyte marker) and anti-CERS6 antibodies.
Results
Univariate and multivariate analyses revealed significant changes in lipid species involved in Cer metabolism within the glomeruli of aging marmosets. Notably, C16 Cer accumulated in the glomeruli of aged marmosets. The enzyme CERS6, which biosynthesizes C16 Cer, was significantly elevated in the kidney cortex of aging marmosets compared to young controls. IF demonstrated that CERS6 was specifically expressed in podocytes of marmoset kidneys and its expression increased with age.
Conclusion
These findings indicate dysregulation of Cer metabolism in the glomeruli (e.g., podocytes) of aging marmoset kidneys. This provides valuable insights into potential therapeutic targets and enhances our understanding of the pathological and metabolic changes associated with renal aging.
Funding
- Other NIH Support