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Abstract: FR-PO1059

The Acute-Phase Protein α1-Acid Glycoprotein Ameliorates Proteinuria Through Maintaining Renal Endothelial Barrier Function and Modulating Macrophages Polarization in Proteinuric Kidney Disease

Session Information

Category: Glomerular Diseases

  • 1202 Glomerular Diseases: Immunology and Inflammation

Authors

  • Fujimura, Rui, Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto-shi, Japan
  • Nishida, Kento, Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto-shi, Japan
  • Bi, Jing, Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto-shi, Japan
  • Watanabe, Hiroshi, Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto-shi, Japan
  • Maruyama, Toru, Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto-shi, Japan
Background

Proteinuria is the hallmark of progressive chronic kidney disease (CKD). It is highly desired to develop an effective strategy that prevents glomerular filtration barrier injury and renal inflammation which can cause proteinuria. The acute phase plasma protein, α1-acid glycoprotein (AGP) is a component of glomerular endothelial barrier and contributes to maintaining an intact barrier. In addition, we have previously showed that AGP has anti-inflammatory action via up-regulating CD163 in macrophage. The purpose of this study is to evaluate the renoprotective effect of exogenously administered-AGP against adriamycin-induced nephropathy (AN), a model of chronic proteinuric renal disease.

Methods

AN-mice were created by the administration of 15mg/kg of adriamycin. AGP was administered to AN mice (iv) from day 1 to day 5. Mice were sacrificed on day 7 or 21. Renal function, structural injury and inflammation were evaluated. The renal glomerular distribution of exogenous administered AGP was examined by immunostaining using anti-AGP antibody. To investigate the effect of AGP on macrophage polarization, in vitroexperiments were performed using PMA-differentiated THP-1 cells.

Results

AGP administration ameliorated AN-induced proteinuria, histological changes and macrophage infiltration in renal tissue. We also found the decreased distribution of endogenous AGP on the glomerulus in AN-mice, but this decrease was recovered by the administration of exogenous AGP. In kidney of AGP-treated mice, increased mRNA expression of CD163, M2 macrophage marker, and decreased mRNA expression of iNOS, M1 macrophage marker, were observed. To confirm this finding in vitro, we investigated the effect of AGP on THP-1-derived macrophage polarization. The data showed that AGP treatment significantly increased CD163 mRNA expressions, while it decreased iNOS mRNA expression, suggesting that AGP could be able to modulate the macrophage phenotype to anti-inflammatory potential.

Conclusion

AGP ameliorates proteinuria through maintaining renal endothelial barrier function and modulating macrophages polarization.