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Abstract: TH-PO891

Basigin/CD147 Exacerbates Diabetic Kidney Disease Dependent of Proteinuria

Session Information

Category: Diabetic Kidney Disease

  • 601 Diabetic Kidney Disease: Basic

Authors

  • Watanabe, Tomoharu, Nagoya University, Nagoya, Japan
  • Kosugi, Tomoki, Nagoya University Graduate School of Medicine, Nagoya, Japan
  • Ryuge, Akihiro, Nagoya University Graduate School of Medicine, Nagoya, Japan
  • Masuda, Tomohiro, Nagoya University Graduate School of Medicine, Nagoya, Japan
  • Maeda, Kayaho, Nagoya University Graduate School of Medicine, Nagoya, Japan
  • Kato, Sawako, Nagoya University Graduate School of Medicine, Nagoya, Japan
  • Maruyama, Shoichi, Nagoya University Graduate School of Medicine, Nagoya, Japan
Background

CD147/Basigin (Bsg), a glycosylated transmembrane protein, contributes to cell survival, migration, cancer invasion and inflammation. We have so far demonstrated its pathophysiological roles in the kidney diseases, ranging from the occurrence of acute kidney injury accompanied by ischemia to progression of renal fibrosis and lupus nephritis. However, the mechanism of diabetic kidney disease (DKD) involving Bsg remains unknown. We therefore focused on Bsg function in the development of DKD with proteinuria.

Methods

Two independent mice models were performed using wild-type (Bsg+/+) or Bsg-deficient (Bsg-/-) mice treated with streptozotocin or overloaded by bovine serum albumin, respectively. Primary proximal tubular epithelial cells (PTECs) derived from Bsg+/+ or Bsg-/- mice and human PTECs were exposed to high glucose (30mM) or albumin. In clinical study, DKD patients (N=52) registered with UMIN Clinical Trials Registry (8016) were treated with spironolactone 25 mg once daily for 8 weeks. The relationships between urinary Bsg values and clinical indicators were examined.

Results

While Bsg-/- mice induced by protein overload ameliorate the development of tubulointerstitial injury, no obvious difference in the two genotypes representing DKD was found. In clinical study, DKD patients showed higher plasma and urinary Bsg values and marked Bsg inductions in injured tubulointerstitium. Plasma and urinary Bsg levels showed close correlations with eGFR and proteinuria, but not HbA1c, respectively. DKD patients treated with spironolactone showed a striking reduction of urinary Bsg values as well as albuminuria. A close association between reduction rates of urinary Bsg values and albuminuria was observed. In in vitro study, Bsg inductions in primary PTECs after exposure of albumin, but not high glucose, were found in a concentration-dependent fashion. Bsg silencing and gene deficiency in PTECs limited inflammation-related chemotactic activation such as MMPs and MCP-1.

Conclusion

Bsg plays an indispensable role in the development of DKD evoked by proteinuria through the activation of inflammatory signaling.