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Abstract: SA-PO987

RNAomics of APOL1 Risk and Non-Risk Allele Expressing Podocytes in HIV Milieu

Session Information

Category: Glomerular Diseases

  • 1403 Podocyte Biology

Authors

  • Johal, Prabhjot Kaur, Post Graduate Institute of Medical Education and Research, Chandigarh, Chandigarh, India
  • Kumar, Vinod, Post Graduate Institute of Medical Education and Research, Chandigarh, Chandigarh, India
  • Skorecki, Karl, Bar-Ilan University, Ramat Gan, Tel Aviv, Israel
  • Ramachandran, Raja, Post Graduate Institute of Medical Education and Research, Chandigarh, Chandigarh, India
  • Malhotra, Ashwani, Northwell Health Feinstein Institutes for Medical Research, Manhasset, New York, United States
  • Singhal, Pravin C., Northwell Health Feinstein Institutes for Medical Research, Manhasset, New York, United States
Background

African Americans (AAs) develop chronic kidney diseases (CKD) at 4-5 folds higher rates than European Americans (EAs), and this disparity is over 10 folds in the case of HIV-associated nephropathy (HIVAN), which is predominantly related to two risk alleles (G1 and G2) in APOL1 gene in AAs. To explore the underlying molecular mechanisms, we evaluated the gene expression profiles in podocytes expressing APOL1-G0 (wild-type), G1, and G2 in the HIV milieu.

Methods

Stably expressing APOL1-G0, G1, or G2 cell lines were transduced with HIV, followed by the extraction of RNAs and RNA-seq analysis.

Results

All cells expressed comparable RNA and protein expression of APOL1, but G1- and G2-podocytes displayed attenuated nephrin expression (a marker of podocyte health) in the HIV milieu. RNA-seq analysis showed similar gene expression alterations in G1- and G2-podocytes, their expression profiles differed from that in G0-podocytes. KEGG pathway enrichment analysis revealed predominant alterations in inflammation-regulating signaling pathways such as MAPK, NF-kappa B, phospholipase D, NOD-like receptor, and Fc epsilon RI in G-1 and G2- podocytes when compared with G0-podocytes.

Conclusion

These findings suggest that AAs may suffer from a higher occurrence of CKD due to enhanced inflammatory milieu in podocytes caused by APOL1 risk alleles. Our study provides insight into the underlying molecular mechanisms in developing APOL1-associated nephropathy.

All cells expressed comparable RNA (Figure A) and protein expression of APOL1 (Figure B), but G1- and G2-podocytes displayed downing of podocyte nephrin expression in HIV milieu. RNA-seq analysis showed that G1- and G2-podocyte expression profiles were disparate from that in G0-podocytes (Figure C). KEGG pathway enrichment analysis revealed that compared with APOL1-G0, the risk alleles G1 and G2 mainly altered inflammation regulating signaling pathways (Figure D).

Funding

  • NIDDK Support