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Abstract: FR-PO214

Salvianolate Ameliorates Oxidative Stress and Podocyte Injury Through Modulation of AMPK/NOX4 Axis in db/db Mice

Session Information

Category: Diabetic Kidney Disease

  • 601 Diabetic Kidney Disease: Basic

Authors

  • Dai, Yan, Zhongshan Hospital, Fudan University, ShangHai, China
  • Liang, Yiran, Zhongshan Hospital, Fudan University, ShangHai, China
  • Fang, Yi, Zhongshan Hospital, Fudan University, ShangHai, China

Group or Team Name

  • Division of Nephrology, zhongshan hospital, fudan university
Background

Changes in podocyte morphology and function are associated with albuminuria and progression of diabetic nephropathy (DN). NADPH oxidase 4 (NOX4) is the main source of reactive oxygen species (ROS) in the kidney and NOX4 is upregulated in podocytes in response to high glucose.

Methods

In the present study, the effects of Salvianolate on DN and its underlying mechanisms were investigated in diabetic db/db mice and human podocytes.

Results

We confirmed that Salvianolate injection administration exhibited similar beneficial preventive results with the NOX1/NOX4 inhibitor, as reflected by attenuated albuminuria, reduced podocyte loss and mesangial matrix accumulation. We further observed that Salvianolate exerted its renoprotective role via reducing high-glucose induced NOX4-based NADPH oxidase activity, podocyte apoptosis and restoring podocyte differenation marker (synptopodin) expression in the isolated glomeruli of db/db mice. In human podocyte, NOX4 was expressed in the mitochondrial compartment and Salvianolate treatment blocked NOX4-derived mitochondrial superoxide generation and activated AMPK kinase expression, thereby ameliorating podocyte apoptosis. Therefore, Salvianolate possesses the renoprotective capabilities in part through AMPK-mediated control of NOX4 expression, confirmed by AMPK inhibitor (Compound C).

Conclusion

Taken together, our results identify that Salvianolate could prevent glucose-induced oxidative podocyte injury through modulation of AMPK/NOX4 axis in DN and have a novel therapeutic potential for DN.

Funding

  • Government Support - Non-U.S.