Abstract: SA-PO764
Basigin/CD147 Facilitates Uptake of Protein into Renal Tubular Epithelium
Session Information
- CKD: Mechanisms - III
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2103 CKD (Non-Dialysis): Mechanisms
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
- Maeda, Kayaho, Nagoya University Graduate School of Medicine, Nagoya, Japan
- Sato, Yuka, Nagoya University Graduate School of Medicine, Nagoya, Japan
- Kato, Noritoshi, Nagoya University, 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, plays a crucial role in processes such as cancer development, inflammation and immune system regulation. We have so far demonstrated that Bsg is involved in the pathogenesis of acute kidney injury and renal fibrosis. In the injured kidneys, this expression is induced strongly in the basolateral sides of TECs, infiltrating inflammatory cells. In a series of prior clinical studies, proteinuric kidney diseases such as minimal change nephrotic syndrome, showed marked increases in urinary Bsg levels, and a close relationship between proteinurea and urinary Bsg levels. Aberrant molecular mechanisms involving Bsg-mediated intracellular metabolism may be a crucial determinant of proteinuric tubular injury. In this study, we investigated whether Bsg deficiency maintains intracellular homeostasis by inhibiting uptake of protein into TECs.
Methods
As a clinical study, diabetic kidney disease (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. We then induced tubulointerstitial injuries in wild-type (Bsg+/+) or Bsg-deficient (Bsg-/-) mice using intraperitoneal injections of a large amount of protein for 14 days. Immortalized proximal tubule epithelial cell line from normal adult human kidney (HK2) was exposed to high glucose (40mM) or bovine serum albumin (BSA).
Results
In DKD patients, plasma and urinary CD147 levels showed a correlation with eGFR or proteinuria, but not HbA1c, respectively. In biopsy tissues of patients with DKD, marked CD147 induction was detected in injured lesions representing renal inflammation. In a basic study, Bsg-/- mice induced by protein overload ameliorate the development of tubulointerstitial injuries and kidney dysfunction. In Bsg+/+ kidneys with protein overload, several apoptotic factors were enhanced with increased Bsg expression. Bsg silencing in HK2 exposed to BSA suppressed uptake of BSA into the epithelium, and decreased heme oxygenase-1 expression as a marker of oxidative stress. Exposure of high glucose wasn’t affected.
Conclusion
Bsg is involved in the pathogenesis of tubulointerstitial injuries by protein overload through promoting uptake of protein into TECs.