Abstract
Acute kidney injury (AKI) induced by cisplatin (cis-AKI) involves indicators such as inflammation and oxidative stress (OS) in proximal tubules, although its underlying mechanisms remain largely unknown so far. Exploration of the molecular mechanisms underlying cisplatin-induced AKI is of great significance for AKI prevention and also for preventing its progression into chronic kidney disease (CKD) or end-stage renal disease (ESRD). OS and ferroptosis are mutually causal; they finally lead to the regulatory cell injury and death induced by the accumulation of reactive oxygen species (ROS). GPX4 is critical not only in OS, but studies established as the key regulator of ferroptosis. In this context, the present study focused on determining the biological function of miR-214-3p in the cisplatin-induced ferroptosis of tubular epithelial cell (TEC) and the underlying molecular mechanism. The relationship between TEC ferroptosis and cisplatin-induced AKI was investigated in vitro and in vivo. Ferrostatin-1(Fer-1), an inhibitor of ferroptosis, was observed to confer a protective effect against the renal tubular injury and renal failure induced by cisplatin. MicroRNAs (miRNAs) regulate the genes that have important functions in the development of cis-AKI. In the present study, GPX4 was predicted as a target of miR-214-3p. Moreover, inhibiting miR-214-3p enhanced the expressions of GPX4 and SLC7A11 while decreasing the ACSL4 expression. Furthermore, miR-214-3p down-regulation protected against TEC death and renal tubule damage both in vitro and in vivo. According to these findings, inhibiting miR-214-3p would alleviate TEC ferroptosis in cis-AKI via GPX4.