Astragaloside IV protest against podocyte injury through upregulating mitophagy via Mfn2/ Pink 1/Parkin axis

Abstract Background Podocyte injury is the most important pathological hallmark of kidney diseases, Autophagy is the critical factors that involve podocyte injury. here we sought to determine whether astragaloside IV (AS-IV) was able to improve renal function and reverse podocyte injury through regulation of autophagy. Methods Using Adriamycin (ADR) mice model and cultured immortalized mouse podocytes, were exposed to AS-IV. Western blotting, immunofluorescence and histochemistry were used to analyze markers of autophagy, mitochondrial dysfunction, podocyte apoptosis and glomerulopathy in the progression of focal segmental glomerular sclerosis. Results We observed that AS-IV can inhibit podocyte apoptosis, increased reactive oxygen species (ROS) generation, mitochondrial fragmentation and dysfunction through inducing Mitofusin 2(Mfn2)/ PTEN induced putative kinase 1(PINK1)/Parkin mitophagy pathway both in vivo and in vitro. Over-expression of Mfn2 reduced puromycin aminonucleoside (PAN)-induced podocyte injury, while down regulation of Mfn2 expression limited the renal protective effect of AS-IV through regulating mitophagy. Conclusion AS-IV ameliorates renal function and renal pathological changes in ADR mice and inhibits PAN-induced podocyte injury by directly enhancing PINK1/Parkin/Mfn2 associated autophagy.