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Abstract: TH-PO978

Pathological Characteristics of USAG-1 and BMP-7 Expression in Rats with CsA nephrotoxicity

Session Information

Category: Pathology and Lab Medicine

  • 1501 Pathology and Lab Medicine: Basic

Authors

  • Sugimoto, Keisuke, kindai University Faculty of Medicine, Izumi, osaka-fu, Japan
  • Miyazaki, Kohei, kindai University Faculty of Medicine, Izumi, osaka-fu, Japan
  • Enya, Takuji, kindai University Faculty of Medicine, Izumi, osaka-fu, Japan
  • Miyazawa, Tomoki, kindai University Faculty of Medicine, Izumi, osaka-fu, Japan
  • Okada, Mitsuru, kindai University Faculty of Medicine, Izumi, osaka-fu, Japan
  • Takemura, Tsukasa, Kushimoto municipality hospital, Wakayama, Japan
Background

CsA-nephrotoxicity is associated with decreased renal bone morphogenetic protein-7 (BMP-7) expression. Uterine sensitization-associated gene-1 (USAG-1), a kidney-specific BMPs antagonist, plays an important role in processing renal damage. The study aimed to evaluate the renal expression of USAG-1 and BMP-7 induced by CsA in a rat model.

Methods

Eight BrlHan:WIST@Jcl (GALAS) rats were assigned to two groups: control (untreated) and CsA (orally received CsA 10 mg/kg body weight). After 28 days, the renal tissues were examined for CsA toxicity, specifically, tubulointerstitial damage and arteriolopathy, by light microscopy. Furthermore, the area of USAG-1 and BMP-7 expression was scored by immunohistochemical staining.

Results

The CsA group showed mild interstitial fibrosis, but no arteriolohyalization and tubular atrophy. Two of the 4 rats in the CsA group presented findings similar to those observed during the early stage of focal segmental glomerulosclerosis (FSGS) development, such as enlargement of glomeruli and foam cells. In these 2 rats, high focal USAG expression and significantly decreased BMP-7 expression were also noted. In contrast, a broad area with BMP-7 expression was observed in the kidney of the 2 rats from the CsA group that presented fewer FSGS-like findings and in the control rats (no CsA nephrotoxicity).

Conclusion

In this study, the characteristic histologic changes of CsA-nephrotoxicity were not observed, but FSGS-like findings were noted. USAG expression may contribute to BMP-7 suppression, resulting in FSGS-like pathology that leads to CsA-nephrotoxicity. Furthermore, an imbalance in USAG-1 and BMP-7 expression may also be involved in CsA-induced nephrotoxicity.