Abstract: SA-PO229

Vangl2 Is Associated with Ephrin-B1, a Novel Critical Component of the Slit Diaphragm, and Its Downregulation Is Involved in the Initiation Event of the Podocyte Injury

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

  • Fukusumi, Yoshiyasu, Dept. Cell Biology, Kidney Research Center, Niigata University, Niigata, Japan
  • Zhang, Ying, Dept. Cell Biology, Kidney Research Center, Niigata University, Niigata, Japan
  • Kawachi, Hiroshi, Dept. Cell Biology, Kidney Research Center, Niigata University, Niigata, Japan
Background

Podocyte-specific ephrin-B1 conditional knockout (CKO) mice showed proteinuria and disarrangement of the slit diaphragm (SD) molecules. However, the interaction of ephrin-B1 with other podocyte molecules is not well analyzed. To identify the molecules related with ephrin-B1, the gene expression profile in glomeruli of the CKO mice was analyzed by RNA-seq. The profile showed 260 molecules were downregulated to less than 50% in glomeruli of the CKO mice. We found a planar cell polarity protein vangl2 was evidently downregulated. It is reported that vangl2 plays an important role in podocyte maturation. However, the interaction of vangl2 with ephrin-B1 and the role of vangl2 in the development of nephrotic syndrome were not investigated.

Methods

The expression of vangl2 and its interaction with ephrin-B1 and other SD molecules were analyzed in glomeruli of the ephrin-B1 CKO mice and three types of rat nephrotic models, the SD specific injury caused by the anti-nephrin antibody (ANA), puromycin aminonucleoside (PAN) nephropathy, a mimic of MCNS, and adriamycin (ADR) nephropathy, a mimic of FSGS.

Results

The decrease of vangl2 mRNA expression in glomeruli of the ephrin-B1 CKO mice was confirmed by the qRT-PCR (33 ± 21% to control, p < 0.01). The immuno-staining of vangl2 was evidently decreased in the CKO mice. In ANA nephropathy, mRNA expression of vangl2 was already decreased at 1 h (1h, 27%, p < 0.05; day 1, 13%, p < 0.01; day 5, 34%, p < 0.05). The intensity of the vangl2 staining clearly decreased at 1 h when the nephrin staining was not decreased yet. The staining of vangl2 decreased also in PAN nephropathy, although the mRNA expression was not altered. In ADR nephropathy, the intensity of the vangl2 staining was clearly decreased on day 7 and 28. By contrast, the mRNA expression of vangl2 was upregulated.

Conclusion

Vangl2 was clearly downregulated in the ephrin-B1 CKO mice. The decrease of the vangl2 staining in the nephrotic models advances the decrease of the expressions of ephrin-B1, nephrin and other SD molecules. It is plausible that the alteration of vangl2 expression is involved in the initiation event of the nephrotic syndrome. Vangl2 could be an early marker to detect podocyte injury.

Funding

  • Government Support - Non-U.S.