Abstract
Podocyte injury underlies many forms of glomerular diseases. Our previous study showed that hyperoside, a naturally occurring flavonoid, could decrease albuminuria at the early stage of diabetic nephropathy by ameliorating renal damage and podocyte injury. However, its protective mechanism against podocyte injury is unknown. A previous study demonstrated that hyperoside might inhibit amyloid β-protein-induced neurotoxicity by suppressing mitochondrial dysfunction. Both mitochondrial dysfunction and its upstream determinant mitochondrial fission were closely related to podocyte injury. Thus, in the current study, we tested the effect of hyperoside on mitochondrial dysfunction and mitochondrial fission in adriamycin (ADR)-induced podocyte injury. In the mice model of ADR-induced nephropathy, hyperoside treatment inhibited ADR-induced albuminuria and podocyte injury. Meanwhile, hyperoside also blocked ADR-induced mitochondrial dysfunction and mitochondrial fission. Consistently, in cultured human podocytes, hyperoside suppressed ADR-induced podocyte injury, mitochondrial dysfunction and mitochondrial fission. All these results indicated that hyperoside might inhibit ADR-induced mitochondrial dysfunction and podocyte injury through suppressing mitochondrial fission both in vivo and in vitro. The underlying mechanisms which we revealed support the therapeutic effects of hyperoside for a broad range of glomerular diseases.
Highlights
Podocytes, which are highly specialized, terminally differentiated epithelial cells lining the outer surface of the glomerular capillaries, serve as a critical size and charge barrier to prevent proteinuria [1]
Hyperoside prevented renal structural changes and albuminuria in adriamycin mice To determine the effect of hyperoside in adriamycin nephropathy, we examined the kidneys of these mice histopathologically
In the mitochondrial fraction, we found that dynamin-related protein 1 (Drp1) increased significantly in the ADR group compared with the control group, which was blocked by hyperoside (Figure 4B)
Summary
Podocytes, which are highly specialized, terminally differentiated epithelial cells lining the outer surface of the glomerular capillaries, serve as a critical size and charge barrier to prevent proteinuria [1]. Independent laboratories have reported that podocyte injury plays an essential role in causing the defective glomerular filtrations and the onset of proteinuria [2]. Regardless of the diverse origins of glomerular diseases, podocytes are critical determinants in www.impactjournals.com/oncotarget the progression of all glomerular diseases [3]. Exploration of pathogenic mechanisms of podocyte injury is important for the future treatment. Our previous study demonstrated that mitochondrial dysfunction mediated aldosterone-induced podocyte injury [4]. Targeting mitochondria may offer a novel approach to reduce podocyte injury
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