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Abstract: SA-PO341

miR193a-VDR/RXR Axis and Renin Expression in the Transition of Parietal Epithelial Cells to Podocytes

Session Information

Category: Development, Stem Cells, and Regenerative Medicine

  • 600 Development, Stem Cells, and Regenerative Medicine

Authors

  • Kumar, Vinod, 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

Loss of kidney cells is a predominant cause of impaired kidney function in aging kidneys. Renin-expressing cells make a pool of renal progenitor cells, where the lack of renin expression determines their differentiation potential. Since microRNAs are the regulators of gene expression, we analyzed the role of the mir193a-VDR/RXR axis in regulating the renin expression and the stemness of Parietal Epithelial cells (PECs).

Methods

Human PECs were grown and analyzed for the expression of miR193a, renin, VDR, and RXR using real-time PCR and Western blotting. PECs were transitioned to podocytes by transfecting either miR193a plasmid or an inhibitor of miR193a. The PECs transition potential was also analyzed under the overexpression of VDR and RXR. Immunoprecipitation assays were performed to evaluate the potential interaction of VDR/RXR and Renin. Luciferase experiments were carried out to elucidate the binding of miR193a to VDR 3'UTR. In vivo, studies were carried out in control (Balb/C) and miR193a transgenic mice.

Results

Differentiated podocytes (DPD)-overexpressing (OE) VDR showed enhanced expression of VDR and podocyte markers but a decreased renin expression (Figure A). Renal tissues of miR193a transgenic mice not only showed attenuated podocyte markers (Nephrin, podocalyxin [PDX], WT1) and VDR/RXR but also showed enhanced renin expression when compared to control mice (Figures B and C). The miR193a expression inversely regulated the VDR expression, and the downing of VDR prevented hetero-dimerization with RXR contributing to poor reprogramming of PECs.

Conclusion

miR193a-VDR/RXR regulates renin expression and determines the efficient transition of PECs to podocytes.

A. Protein blots of differentiated podocytes (DPD) -overexpressing (OE) VDR were probed podocyte markers and renin. B. Protein blots of renal tissues of control (Balb/C) and miR193a transgenic mice were probed podocyte markers (Nephrin, PDX, WT1), VDR/RXR, renin and Angiotensinogen (Ang) expression. C. Immunolabeling of renal cortical sections of mice for VDR and renin.

Funding

  • NIDDK Support