期刊
FRONTIERS IN MEDICINE
卷 8, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fmed.2021.803874
关键词
HIF-1 alpha; mitophagy; diabetic nephropathy; inflammation; ROS; apoptosis
资金
- National Natural Science Foundation of China [U1904134]
- Henan Province Young and Middle-aged Health Science and Technology Innovative Talents (Leader) Project [YXKC2020014]
HIF-1 alpha-mediated mitophagy plays a protective role in diabetic nephropathy, preventing apoptosis and ROS production.
It is well-established that mitophagy leads to Diabetic Nephropathy (DN) and renal failure. Mitophagy mediated by a Hypoxia-inducible factor-1 alpha (HIF-1 alpha) plays a beneficial role in many diseases. Nevertheless, the mechanisms underlying HIF-1 alpha-mediated mitophagy in DN remain unclear. This study defines the role of HIF-1 alpha mediated mitophagy in DN. The expression of HIF-1 alpha was upregulated in HK-2 cells in an High-Glucose (HG) environment, and the YC-1 (a specific inhibitor of HIF-1 alpha) further exacerbated the hypoxia-induced mitochondrial dysfunction. Conversely, the HIF-1 alpha-mediated protective effect was strengthened by scavenger N-acetylcysteine (NAC), a type of reactive oxygen species. Moreover, HIF-1 alpha-Parkin/PINK1-mediated mitophagy prevented apoptosis and ROS production in HK-2 cells subjected to HG exposure. In summary, HIF-1 alpha mediated mitophagy on HK-2 cells under HG conditions could alleviate DN, suggesting that it has huge prospects for DN treatment.
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