Abstract: TH-PO066

Isthmine-1, a New Podocyte Protein Involved in the Progression of Nephrotic Syndrome

Session Information

Category: Glomerular

  • 1002 Glomerular: Basic/Experimental Pathology

Authors

  • Boffa, Jean-Jacques, Tenon Hospital, AP-HP, Paris, France
  • Zhang, Lu, Jiangsu Province Hospital of Chinese Medcine, Nanjing, China
  • Marie aude, Sahiri Virgilia, INSERM U1155 / UPMC, Paris, France
  • Ghachem, Khalil Ahmed, INSERM U1155, Paris, France
  • Sandrine, Placier, INSERM 1155 - UPMC, Paris , France
  • Jouanneau, Chantal, inserm, Paris 20, France
  • Chatziantoniou, Christos, Tenon Hospital, Paris, France
Background

Using differential transcriptomic analysis in renal cortical slices from hypertensive rats with nephrotic level of proteinuria, we identified and studied isthmine-1 (ISM-1), a new player of renal diseases.

Results

Under control physiological conditions, ISM-1 is strongly expressed and colocalized with nephrin in rodents and humans as well. Immunogold electron microscopy revealed that ISM-1 localizes on podocyte foot processes. Because its two receptors, avb5integrin and grp78 (Bip) are involved in podocytopathy, we induced nephrotic syndrome in rats by PAN and doxorubicine injection. In both experimental models, we found increased expression of ISM-1 mRNA and protein on isolated glomeruli. Likewise, the expressions of its two receptors were increased and contrasted to the decrease of nephrin protein expression. In addition, ISM-1 expression increased after doxorubicine stimulation in primary cultured podocytes in vitro. To determine the role of ISM-1, ISM-1 antisens ODN were administered in experimental models of nephrotic syndrome in vivo. Although ISM-1 antisens administration blunted ISM-1 expression, no difference was observed in the progression and severity of the disease in PAN rats. Because, ISM-1 has been shown to act as a permeability factor during lung sepsis, we are pursuing our studies by examining its role on glomerular membrane permeability.

Conclusion

Our results show the discovery of a novel protein ISM-1 specifically expressed in podocyte in normal conditions. This expression is further increased in the progression of nephrotic syndrome. We are currently investigating the physiopathological role of this increase.