Affiliation:
1. Department of Nephrology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, China
2. Key Laboratory of Zhejiang Province, Management of Kidney Disease
3. Key Laboratory of Precise Prevention and Treatment of Rheumatism Syndrome of renal Wind Disease
Abstract
Background:
Podocyte injury is the most important pathological hallmark of
kidney diseases. Autophagy is a critical factor that involves podocyte injury. Here, we
sought to determine whether Astragaloside IV (AS-IV) was able to improve renal
function and reverse podocyte injury through the regulation of autophagy.
Methods:
Using the Adriamycin (ADR) mice model, 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 by
inducing the Mfn2/Pink1/Parkin mitophagy pathway both in vivo and in vitro. Overexpression
of Mfn2 reduced puromycin aminonucleoside (PAN)-induced podocyte
injury, while downregulation of Mfn2 expression limited the renal protective effect of
AS-IV by regulating mitophagy.
Conclusion:
AS-IV ameliorates renal function and renal pathological changes in ADR
mice and inhibits PAN-induced podocyte injury by directly enhancing
Mfn2/Pink1/Parkin-associated autophagy.
Publisher
Bentham Science Publishers Ltd.