Abstract
It is well-established that mitophagy leads to Diabetic Nephropathy (DN) and renal failure. Mitophagy mediated by a Hypoxia-inducible factor-1α (HIF-1α) plays a beneficial role in many diseases. Nevertheless, the mechanisms underlying HIF-1α-mediated mitophagy in DN remain unclear. This study defines the role of HIF-1α mediated mitophagy in DN. The expression of HIF-1α was upregulated in HK-2 cells in an High-Glucose (HG) environment, and the YC-1 (a specific inhibitor of HIF-1α) further exacerbated the hypoxia-induced mitochondrial dysfunction. Conversely, the HIF-1α-mediated protective effect was strengthened by scavenger N-acetylcysteine (NAC), a type of reactive oxygen species. Moreover, HIF-1α-Parkin/PINK1-mediated mitophagy prevented apoptosis and ROS production in HK-2 cells subjected to HG exposure. In summary, HIF-1α mediated mitophagy on HK-2 cells under HG conditions could alleviate DN, suggesting that it has huge prospects for DN treatment.
Highlights
The development of the global economy has been paralleled by lifestyle changes, resulting in an elevated incidence of type 2 diabetes mellitus, which has gradually became a serious public health and safety concern worldwide [1]
These results indicate that Hypoxia-inducible factor-1α (HIF-1α) may play a role in mitochondrial autophagy in HK-2 cells exposed to the HG environment
We investigated whether a HIF1α-Parkin/PINK1mediated mitophagy exerted a protective effect by decreasing apoptosis and reactive oxygen species (ROS) production in HK-2 cells exposed to the HG environment
Summary
The development of the global economy has been paralleled by lifestyle changes, resulting in an elevated incidence of type 2 diabetes mellitus, which has gradually became a serious public health and safety concern worldwide [1]. Diabetic tubulopathy has an extensive-expression in DN development which contributes to initial renal injury in the pathogenesis of DN [5, 6]. Renal tubular hypoxia is reportedly a pathological change found in the early and advanced stages of DN [7], eing an important pathogenic factor causing renal fibrosis. An increasing body of evidence suggests that high glucose levels upregulate HIF-1α expression in animal models and human renal proximal tubular cells of type 2 diabetes mellitus nephropathy [11,12,13]. The precise role of HIF-1α of diabetic nephropathy in the etiopathogenesis remains unclear
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