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Kidney Week

Abstract: PO0914

PLVAP as a Novel Marker for Endothelial Injury in Diabetic Nephropathy

Session Information

Category: Diabetic Kidney Disease

  • 601 Diabetic Kidney Disease: Basic

Authors

  • Wolf, Elena Elisabeth, Division of Nephrology, Department of Internal Medicine III, University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany
  • Steglich, Anne, Division of Nephrology, Department of Internal Medicine III, University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany
  • Kessel, Friederike, Division of Nephrology, Department of Internal Medicine III, University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany
  • Gembardt, Florian, Division of Nephrology, Department of Internal Medicine III, University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany
  • Sradnick, Jan, Division of Nephrology, Department of Internal Medicine III, University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany
  • Reichelt-Wurm, Simone, Department of Nephrology, University Hospital Regensburg, Regensburg, Germany
  • Eidenschink, Kathrin, Department of Nephrology, University Hospital Regensburg, Regensburg, Germany
  • Banas, Miriam C., Department of Nephrology, University Hospital Regensburg, Regensburg, Germany
  • Hugo, Christian, Division of Nephrology, Department of Internal Medicine III, University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany
  • Todorov, Vladimir T., Division of Nephrology, Department of Internal Medicine III, University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany
Background

Diabetic nephropathy (DN) is associated with endothelial cell dysfunction and progressive loss of kidney function. The plasmalemma vesicle associated protein (PLVAP) has been found to be necessary for the formation of endothelial diaphragms in fenestrae, caveolae, and transendothelial channels. In the adult kidney, glomerular endothelial cells lack diaphragms in the fenestrae. Previous studies reported glomerular expression of PLVAP in transplant glomerulopathy, in mesangioproliferative glomerulonephritis model and in mice developing renal thrombotic microangiopathy as a consequence of defective Gsα/cAMP signaling in renin cells. Therefore, we investigated whether PLVAP expression in glomerular capillaries is induced in different models of DN.

Methods

To induce a model of type 1 diabetes, one dose of streptozotocin (STZ, 180 mg/kg) was administered by intraperitoneal injection in 6-8 weeks old mice. 16-week-old black and tan brachyuric (BTBR) ob/ob mice, with spontaneous mutation in the leptin gene were used as a model of type 2 diabetes. Immunohistochemical staining and analysis was performed to examine the expression of PLVAP. We co-stained the Intercellular Adhesion Molecule 2 (ICAM2) as a marker for endothelial cells.

Results

Glomerular hypertrophy was found in STZ mice and BTBR ob/ob mice, which was interpreted as evidence for successful induction of DN (STZ: 2750 µm2, control: 2527 µm2; BTBR ob/ob: 4471 µm2, control: 2295 µm2). Using immunohistochemical analysis, the BTBR ob/ob mice and the STZ mice revealed induced PLVAP expression in their glomeruli, as compared with non-diabetic controls (p<0.05 respectively). ICAM2 expression in glomeruli of STZ mice tended to be lower than in control mice, but the difference was not statistically significant. In BTBR ob/ob mice, the expression of ICAM2 was significantly decreased compared to control mice (p<0.05).

Conclusion

Our results indicate that the glomerular expression of PLVAP is induced in diabetic nephropathy. The protein PLVAP represents a potential novel marker for endothelial injury in diabetic nephropathy.

Funding

  • Private Foundation Support