Abstract: TH-PO477
Apolipoprotein M Treatment Restores Kidney Function in Mouse Model of Alport Syndrome
Session Information
- Genetic Diseases: Glomerulopathies - I
November 02, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1202 Genetic Diseases of the Kidneys: Non-Cystic
Authors
- Molina David, Judith T., University of Miami Katz Family Division of Nephrology and Hypertension, Miami, Florida, United States
- Tolerico, Matthew, University of Miami Katz Family Division of Nephrology and Hypertension, Miami, Florida, United States
- Kim, Jin Ju, University of Miami Katz Family Division of Nephrology and Hypertension, Miami, Florida, United States
- Drexler, Yelena, University of Miami Katz Family Division of Nephrology and Hypertension, Miami, Florida, United States
- Merscher, Sandra M., University of Miami Katz Family Division of Nephrology and Hypertension, Miami, Florida, United States
- Fornoni, Alessia, University of Miami Katz Family Division of Nephrology and Hypertension, Miami, Florida, United States
Background
Studies suggest that altered Apolipoprotein M ( APOM) expression is associated with dyslipoproteinemia, atherosclerosis and possibly diabetes, obesity, and inflammation. However, little is known about the role of APOM in the kidney. We previously reported decreased glomerular APOM expression in glomerular diseases. ApoM is a protein linking cholesterol and sphingolipid metabolism, which are both important players in the development of glomerular injury in Alport Syndrome (AS) among other glomerular disorders. Here we test the hypothesis that systemic replacement of ApoM in AS protects from the development of kidney failure.
Methods
To study the role of APOM in the kidney, we analyzed renal APOM expression in a mouse model of progressive renal disease associated with Alport Syndrome (Col4a3 KO mice). We found reduced mRNA and protein expression of APOM in the kidneys of Col4a3 KO mice. To investigate if APOM replenishment would improve renal function in this mouse model, we injected Col4a3 KO mice with recombinant human APOM (rh-APOM). Three groups of mice were studied: (1) Col4a3 +/+ (WT) + vehicle, (2) Col4a3 -/- (KO) + vehicle, and (3) Col4a3 -/- (KO) + rh-ApoM. rh-APOM was administered by weekly intraperitoneal injection starting at 4 weeks of age and until sacrifice at 8 weeks of age.
Results
APOM mRNA and protein expression were markedly reduced in glomeruli and podocytes from Col4a3 KO mice compared to WT mice. Treatment of Col4a3 KO mice with rh-APOM normalized renal APOM levels and prevented the development of renal failure (serum BUN and creatinine), proteinuria (urinary albumin/creatinine ratio), and protected from the development of glomerulosclerosis, tubular atrophy and dilation.
Conclusion
Our results suggest that restoring renal APOM levels in an experimental model of AS protect from renal failure and that treatment with rh-APOM may represent a novel therapeutic strategy for the treatment of glomerular diseases.
Funding
- NIDDK Support