Abstract: PO1972
Sphingomyelin Phosphodiesterase Acid-like 3B (SMPDL3b) Affects Podocyte Lipid Metabolism and Lipid Droplets Formation
Session Information
- Podocyte Biology
October 22, 2020 | Location: On-Demand
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1204 Podocyte Biology
Authors
- Mallela, Shamroop Kumar, Katz Family Division of Nephrology and Hypertension, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida, United States
- Mitrofanova, Alla, Katz Family Division of Nephrology and Hypertension, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida, United States
- Liu, Xiaochen, Katz Family Division of Nephrology and Hypertension, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida, United States
- Macrina, Lorenza, Katz Family Division of Nephrology and Hypertension, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida, United States
- Patel, Devang M., Katz Family Division of Nephrology and Hypertension, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida, United States
- Ducasa, Gloria Michelle, Katz Family Division of Nephrology and Hypertension, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida, United States
- Al-Ali, Hassan, Katz Family Division of Nephrology and Hypertension, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida, United States
- Marples, Brian, University of Rochester, Rochester, New York, United States
- Merscher, Sandra M., Katz Family Division of Nephrology and Hypertension, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida, United States
- Fornoni, Alessia, Katz Family Division of Nephrology and Hypertension, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida, United States
Background
Lipid droplets (LD) play an important role in many biological processes and LD size and number have been linked to several diseases such type 2 diabetes, heart disease, and non-alcoholic fatty liver disease. LD are mainly composed of triglycerides and cholesterol. We previously demonstrated that the accumulation of LDs occurs in glomeruli of experimental models of diabetic kidney disease (DKD), focal segmental glomerulosclerosis (FSGS) and Alport syndrome, and that lipid accumulation in podocytes is one of the factors contributing to disease progression and may be linked to glomerular TNF expression. We furthermore demonstrated that glomerular expression of sphingomyelinase phosphodiesterase like 3b (SMPDL3b), a glycosylphosphatidylinositol (GPI) anchored protein primarily localized at plasma membrane (PM), affects the function of podocytes in FSGS and diabetic kidney disease (DKD).
With this study, we aimed at exploring the role of SMPDL3b in fatty acid uptake and in the formation of LDs ultimately contributing to podocyte damage
Methods
Fatty acid uptake Assay, Lipid droplets isolation, Western blotting, Mass spectrometry, Lipolysis, TNF IV injections.
Results
We demonstrate that decreased SMPDL3b expression (siSMPDL3b) in podocytes is associated with increased FATP5 protein expression, fatty acid uptake and an increased number of LDs. The number of LDs was decreased in podocytes with increased SMPDL3b expression (SMPDL3b OE). Similarly, TAGs and CE contents were increased in siSMPDL3b when compared to control podocytes. Finally, we demonstrate for the first time that SMPDL3b is present in isolated LDs suggesting a possible role for SMPDL3b in the formation of LDs and/or in lipolysis. In vivo, podocyte specific induction of SMPDL3b is sufficient to protect from TNF induced podocyte injury.
Conclusion
Our results identify a new role of SMPDL3b in the uptake of fatty acids, the accumulation of TAGs, CEs and the formation of LDs. Further experiments to understand the exact mechanism by which SMPDL3b expression contributes to the progression of podocyte damage in FSGS are underway.
Funding
- NIDDK Support