HIF-1α Alleviates High-Glucose-Induced Renal Tubular Cell Injury by Promoting Parkin/PINK1-Mediated Mitophagy

Lu Yu; Yulin Wang; Yan Hong Guo; Liuwei Wang; Zijun Yang; Zi Han Zhai; Lin Tang

doi:10.3389/fmed.2021.803874

HIF-1α Alleviates High-Glucose-Induced Renal Tubular Cell Injury by Promoting Parkin/PINK1-Mediated Mitophagy

Front Med (Lausanne). 2022 Feb 3:8:803874. doi: 10.3389/fmed.2021.803874. eCollection 2021.

Authors

Lu Yu¹, Yulin Wang², Yan Hong Guo¹, Liuwei Wang¹, Zijun Yang¹, Zi Han Zhai¹, Lin Tang¹

Affiliations

¹ First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
² College of Public Health, Zhengzhou University, Zhengzhou, China.

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.

Keywords: HIF-1α; ROS; apoptosis; diabetic nephropathy; inflammation; mitophagy.