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Kidney Week

Abstract: TH-PO809

Bifunctional VDR-miR193a Axis Modulates APOL1 Expression in Human Podocytes

Session Information

Category: Genetic Diseases of the Kidneys

  • 1002 Genetic Diseases of the Kidneys: Non-Cystic


  • Kumar, Vinod, Feinstein Institute of Research, Manhasset, New York, United States
  • Vashistha, Himanshu, Ochsner Health System, New Orleans, Louisiana, United States
  • Ayasolla, Kamesh R., Feinstein Institute for Medical Research, Manhasset, New York, United States
  • Lan, Xiqian, Feinstein Institute for Medical Research, Manhasset, New York, United States
  • Malhotra, Ashwani, Feinstein Institute Medical Research and NSLIJ, Manhasset, New York, United States
  • Skorecki, Karl, Rambam Health Care Campus, Haifa, Israel
  • Singhal, Pravin C., North Shore LIJ Health System, Great Neck, New York, United States

APOL1 plays an important role in the maintenance of podocyte molecular phenotype. We have recently demonstrated that a vitamin D receptor (VDR) agonist (VDA) enhances the expression of APOL1 in human podocytes through down-regulation of miR193a. miR193a plays a vital role in the development of focal segmental glomerulosclerosis (FSGS) both in experimental animal models and humans. miR193a induces oxidative stress and negatively regulate the expression of Wilms Tumor Type (WT) 1 expression in podocytes. We hypothesize that VDR and mir193a inversely regulate each other.


Differentiated immortalized human podocytes (DPDs) and human embryonic kidney cells (HEKs) were treated with different concentrations of a VDR agonist (VDA, EB1089, 0, 5, 10, 50, 100 nM) for 48 hours (n=6); HEKs were transduced with either control or VDR plasmid (n=4); DPDs were transfected with either control of miR193a plasmids (n=4); DPDs were treated with either an empty vector or a specific miR193a inhibitor for 48 hours (n=4). RNAs and proteins were extracted. Protein blots were probed for VDR, APOL1, WT1, and GAPDH. RNAs were assayed for miR193a. cDNAs were amplified for VDR, APOL1, and WT1. To validate the putative binding of mi193a-5p to VDR 3'UTR, Luciferase assay was carried out. To examine the binding of VDR at miR193a promoter, ChiP assay was carried out. To evaluate the role of WT1, HEKs were transfected with control, VDR, or WT1 plasmids and protein blots were probed for VDR, WT1, APOL1, and GAPDH; RNAs were assayed for miR193a.


Both VDA-treated DPDs and HEKs displayed upregulation of APOL1, VDR, and WT1 in a dose-dependent manner. VDR-transfected HEKs as well as DPD-treated with a miR193a inhibitor also showed an increase in APOL1 and WT1 but attenuated miR193a expressions. DPDs overexpressing miR193a showed diminished APOL1, WT1, and VDR expressions (both protein and mRNA). Interestingly, WT1 transfected HEKs showed downregulation of VDR, and VDR-transfected HEKs displayed increased expression of WT1. Luciferase assay showed putative binding sited of miR193a on VDR gene. ChiP assay also showed binding of VDR on miR193a gene. These binding sites suggest that both VDR and miR193a regulate each other.


Bifunctional VDR-miR193a axis regulates APOL1 regulate APOL1 directly as well as through modulation of WT1.


  • NIDDK Support