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Abstract: TH-PO756

Nucleophosmin Translocation Detects Early Podocyte Injury

Session Information

Category: Glomerular Diseases

  • 1403 Podocyte Biology

Authors

  • Urae, Seiya, Boston University, Boston, Massachusetts, United States
  • Wang, Zhiyong, Boston University, Boston, Massachusetts, United States
  • Kumar, Sudhir, Boston University, Boston, Massachusetts, United States
  • Henderson, Joel M., Boston University, Boston, Massachusetts, United States
  • Borkan, Steven C., Boston University, Boston, Massachusetts, United States
  • Beck, Laurence H., Boston University, Boston, Massachusetts, United States
Background

Podocyte loss is common in diverse glomerular diseases. However, the lack of injury markers limits elucidation of the pathophysiologic processes that cause podocyte loss. Nucleophosmin (NPM) mediates regulated kidney cell death, and its translocation from the nucleus to the cytosol is an early marker and trigger of ischemic injury in tubular epithelial cells. Based on these observations, we tested the hypothesis that NPM translocation reflects podocyte injury. In our preliminary study, we detected NPM translocation as a novel marker of podocyte injury in cell injury models, and in human glomerular disease.

Methods

In vitro, podocytes were exposed to diverse insults known to injure podocytes including oxidative stress, adriamycin, and hyper-osmolarity. NPM translocation was evaluated by immunofluorescence and immunoblotting of cytosolic podocyte extracts. To assess NPM translocation in humans, kidney biospy tissue from diabetic nephropathy patients was stained for NPM and established podocyte markers.

Results

NPM translocation was detected in cultured podocytes after oxidative stress, or exposure to either adriamycin, or hyper-osmolarity (Figure 1). Podocyte NPM translocation was also observed in patients with established diabetic kidney disease (Figure 2).

Conclusion

NPM translocation reflects acute podocyte injury in vitro and podocyte injury in diabetic glomerulopathy. Regulated cell death mediated by NPM may be a primary pathologic mechanism of podocyte loss. NPM is also a rational therapeutic target in glomerular diseases to reduce the dropout of the limited number of podocytes residing in the human kidney.