PRMT4 interacts with NCOA4 to inhibit ferritinophagy in cisplatin-induced acute kidney injury

Abstract

Abstract Cisplatin-induced acute kidney injury (AKI) is commonly seen in clinical practice. Ferroptosis, an iron-catalyzed non-apoptotic cell death, is operative in the occurrence of cisplatin-induced AKI. Protein arginine methyltransferase (PRMT4), a member of type I PRMT family, was incorporated in various bioprocesses, but its role in renal injuries has not been investigated. In the present study, we aimed to explore the role of PRMT4 in cisplatin-induced AKI and its mechanism involved. Our data showed that PRMT4 was highly expressed in renal proximal tubular cells, and it was downregulated in cisplatin-induced AKI. Besides, genetic disruption of PRMT4 exacerbated, while its overexpression attenuated, cisplatin-induced redox injuries in renal proximal epithelia. Mechanistically, our work showed that PRMT4 interacted with NCOA4 to inhibit ferritinophagy, a process favoring lipid peroxidation to accelerate ferroptosis. Taken together, our study demonstrated that PRMT4 was bound to NCOA4 to attenuate ferroptosis in cisplatin-induced AKI, suggesting that PRMT4 might present as a new therapeutic target for cisplatin-related nephropathy.