Abstract: SA-PO228

The Role of APOL1 and Cholesterol Dependent Podocyte Injury in Focal Segmental Glomerulosclerosis

Session Information

  • Glomerular: Cell Biology
    November 04, 2017 | Location: Hall H, Morial Convention Center
    Abstract Time: 10:00 AM - 10:00 AM

Category: Glomerular

  • 1003 Glomerular: Cell Biology

Authors

  • Ge, Mengyuan, Katz Family Division of Nephrology and Hypertension, University of Miami Miller School of Medicine, Miami, Florida, United States
  • Sloan, Alexis J., Katz Family Division of Nephrology and Hypertension, University of Miami Miller School of Medicine, Miami, Florida, United States
  • Varona Santos, Javier T., Katz Family Division of Nephrology and Hypertension, University of Miami Miller School of Medicine, Miami, Florida, United States
  • Pedigo, Christopher E., Katz Family Division of Nephrology and Hypertension, University of Miami Miller School of Medicine, Miami, Florida, United States
  • Mendez, Armando, Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, Florida, United States
  • Kopp, Jeffrey B., Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Health, Bethesda, Maryland, United States
  • Merscher, Sandra M., Katz Family Division of Nephrology and Hypertension, University of Miami Miller School of Medicine, Miami, Florida, United States
  • Fornoni, Alessia, Katz Family Division of Nephrology and Hypertension, University of Miami Miller School of Medicine, Miami, Florida, United States
Background

Focal segmental glomerulosclerosis (FSGS) is the most common primary glomerular disorder causing chronic kidney disease (CKD). Susceptibility to FSGS in African Americans is associated with the presence of genetic variants of the Apolipoprotein L 1 gene (APOL1) named G1 and G2. APOL1 is an integral component of high-density lipoprotein (HDL) particles suggesting it might be involved in cholesterol efflux from cells.
We recently established that the pathogenesis of FSGS is linked to tumor necrosis factor (TNF)-mediated, ATP-binding cassette transporters A1 (ABCA1) dependent impairment of cholesterol efflux from podocytes, which are key cells of the glomerular filtration barrier preventing the development of proteinuria in kidney disease. In addition to ABCA1, ABCG1 was shown in other cells to play an important role in cholesterol efflux from cells.

Methods

HeLa cells were stably transfected with lentivirus carrying the APOL1 risk variants under the CMV promoter. Immortalized human urine derived epithelial cells (HUPECs) were established from patients with FSGS carrying different APOL1 genetic variants.

Results

Here we tested the hypothesis that APOL1 confers susceptibility to proteinuric kidney disease by modulating cholesterol efflux from podocytes. We show that APOL1 risk variant expression in HeLa cells leads to decreased cholesterol efflux. The expression of APOL1 risk alleles in HUPECs was not associated with significantly decreased cholesterol efflux from podocytes. However, we observed decreased ABCG1 and APOL1 expression (p<0.01) in the absence of ABCA1 repression. TNF and Interferon (IFN) treatment increased the expression of APOL1 (p<0.001) in urinary podocytes.

Conclusion

Our data reveal that APOL1 risk variant expression may play a role in modulating cholesterol efflux from podocytes, which may contribute to APOL1 mediated genetic susceptibility to FSGS.

Funding

  • NIDDK Support