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Abstract: SA-PO369

Anti-Proteinuria Effect of Antibody Against ANGPTL3 Coiled-Coil Domain on Adriamycin-Induced Nephropathy in Mice

Session Information

Category: Glomerular Diseases

  • 1202 Glomerular Diseases: Immunology and Inflammation

Authors

  • Xu, Hong, Children''s Hospital of Fudan university, Shanghai, China
  • Rao, Jia, Children''s Hospital of Fudan university, Shanghai, China
  • Shen, Qian, Children''s Hospital of Fudan university, Shanghai, China
Background

We firstly found that Angiopoietin-like-3 (Angptl3) expression is increased in glomerular podocytes of nephrotic syndrome. Our previous research showed Angptl3 plays an important role in podocyte injury and proteinuria. This study aims to confirm whether proteinuria in Adriamycin-induced nephropathy mice can be alleviated though neutralizing Angptl3 by antibody.

Methods

The polyantibody against Angptl3-CCD was prepared (namely Anti-angptl3-antibody). Nephropathy was established by Adriamycin injection in 8-12 wk-old female mice. The blockade of Angptl3 by Anti-angptl3-antibody (20mg/kg) was performed every three days for nine times after Adriamycin injection. All mice were sacrificed on day 28. Proteinuria was measured weekly. Albumin, TG and T-CHO in serum were measured on day 28, Histological changes were observed by light microscopy and transmission electron microscope. The distribution of antibody was confirmed by IF analysis.

Results

The Anti-angptl3-antibody can recognize angptl3 specifically. On the 14th day after modeling, proteinuria in the ADR group was significantly increased, but not in ADR plus Anti-angptl3-antibody group until 28th day. The proteinuria of the ADR plus Anti-angptl3-antibody group was significantly lower than that of the ADR group both on the 21th day and 28th(4.46±0.88 vs 11.36±1.00,P=0.010, 21th day; 6.11±1.33 vs 18.97±4.33,P=0.008, 28th day). Compared to the ADR group, serum ALB was higher (p=0.05, n=5), serum CHO (p<0.01, n=5) and TG (p=0.026, n=5) were lower in the ADR plus Anti-angptl3-antibody group. The levels of serum creatinine did not show significantly difference in each group. Focal sclerotic glomeruli were found in the renal tissue of the ADR group, but not found in the ADR plus Anti-angptl3-antibody group. Podocyte injury in the ADR plus Anti-angptl3-antibody group was markedly relieved compared with the ADR group, in which Podocyte foot processes were widely fused. The Anti-angptl3-antibody was detected in the liver and kidney where Angptl3 is expressed in higher amount.

Conclusion

This study demonstrated that Anti-angptl3-antibody can delayed the appearance of proteinuria and decreased the level of proteinuria in Adriamycin-induced nephropathy in mice.