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Abstract: PO0356

Lack of Gb3 Elevated Renal Tubular Injury in a Mouse Model of Aristolochic Acid Nephropathy

Session Information

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Liu, Yang, Boston Children's Hospital Department of Urology, Boston, Massachusetts, United States
  • Tian, Songhai, Boston Children's Hospital Department of Urology, Boston, Massachusetts, United States
  • Thaker, Hatim, Boston Children's Hospital Department of Urology, Boston, Massachusetts, United States
  • Zhang, Jie, Boston Children's Hospital Department of Urology, Boston, Massachusetts, United States
  • Wu, Shan, Jilin University, College of Basic Medical Sciences, Department of Pathology, Changchun, Jilin, China
  • Dong, Min, Boston Children's Hospital Department of Urology, Boston, Massachusetts, United States

Group or Team Name

  • Dong Lab
Background

Globotriaosylceramide (Gb3) is a glycosphingolipid serving as the receptor for Shiga toxin (Stx) and is responsible for mediating binding of Stx onto kidney tissues. However, the normal physiological function of Gb3 in kidney remains unknown. Under normal circumstances, Gb3-knockout (KO) mice (A4GALT (α-1, 4-galactosyltransferase) knockout) showed no obvious physical and chemical abnormalities. Gb3 is known to be mainly distributed in proximal renal tubule and collecting duct epithelial cells in C57 mouse strain, and aristolochic acid (AA), which has nephrotoxic properties, can cause the necrosis in proximal renal tubule epithelial cells. Here we examined whether Gb3 plays a role in AA-induced kidney damage and repair by comparing renal function and pathological changes of wild type (WT) versus A4GALT KO mice after AA challenge.

Methods

WT and A4GALT KO C57 mice were intraperitoneally injected with AA 5mg/kg/d for a total of 8 days. Mice general status and body weight were monitored. The urine, blood, kidney and bladder tissues of the mice were collected on the 9th day to determine the function and pathological changes.

Results

Compared with WT C57 mice, A4GALT KO mice were more sensitive to AA. From day 5 of administration, A4GALT KO mice began to show significant weight loss. On day 9, More severe renal tubular injury pathological changes, significantly increased urine leukocytes and ketones were detected in A4GALT KO mice. The proliferation of bladder transitional epithelial cells was significantly increased in AA treated WT and A4GALT KO C57 mice, accompanied with fibrin deposition, vascular dilatation and a small amount of inflammatory cell infiltration in the bladder compared with that in the untreated group. There was no significant difference in bladder changes between WT and A4GALT KO groups after AA administration.

Conclusion

Our findings uncovered that Gb3 is protective in AA-mediated renal tubular necrosis and its presence reduces kidney injury. We will further explore its specific mechanism in the following study.

Funding

  • Other NIH Support