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Abstract: TH-PO710

Angiotensin II Type 1 Receptor-Associated Protein Ameliorates Streptozotocin-Induced Diabetic Nephropathy in Mice

Session Information

Category: Diabetes

  • 501 Diabetes Mellitus and Obesity: Basic - Experimental

Authors

  • Haruhara, Kotaro, Yokohama City University Graduate School of Medicine, Yokohama, Japan
  • Wakui, Hiromichi, Yokohama City University Graduate School of Medicine, Yokohama, Japan
  • Kobayashi, Ryu, Yokohama City University Graduate School of Medicine, Yokohama, Japan
  • Ohashi, Kenichi, Yokohama City University Graduate School of Medicine, Yokohama, Japan
  • Kurotaki, Daisuke, Yokohama City University Graduate School of Medicine, Yokohama, Japan
  • Tsuboi, Nobuo, The Jikei University School of Medicine, Tokyo, Japan
  • Yokoo, Takashi, The Jikei University School of Medicine, Tokyo, Japan
  • Tamura, Kouichi, Yokohama City University Graduate School of Medicine, Yokohama, Japan
Background

Over-activation of renin-angiotensin system and enhanced infiltration of immune cells are critical factors in the development and progression of diabetic nephropathy (DN). AT1 receptor-associated protein (ATRAP) binds specifically to the AT1 receptor, and suppresses the over-activation of AT1 receptor signals. We have previously shown that ATRAP inhibits hypertension and cardiovascular disease in the animal models of renin-angiotensin system over-activation. Our aim was to determine the protective role of ATRAP in a mouse model of DN.

Methods

Diabetes was induced in wild-type mice (WT) and systemic ATRAP knock-out mice (KO) on a C57BL/6J background by the intraperitoneal injection of streptozotocin (55 mg/kg, daily for 5 consecutive days).

Results

The glycemic and blood pressure status of the diabetic WT and KO were comparable throughout the study period. The urinary albumin excretion was increased and the podocyte number, as estimated by immunohistochemical staining for WT-1, was decreased in the diabetic KO in comparison to the diabetic WT at 24 weeks after the streptozotocin injection (Figure). Furthermore, the renal expression of alternatively activated macrophage-related genes, including Chil3, Arg1, Il4, and Il-13, were suppressed in diabetic KO in comparison to diabetic WT; these macrophages are known to be factors associated with anti-inflammation and tissue repair.

Conclusion

These results suggested that ATRAP plays protective roles in the progression of DN via the maintenance of the renal expression of alternatively activated macrophages, indicating that ATRAP is therefore a novel therapeutic target of DN.