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Updated: Jun 29, 2025
Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes
Published on: January 7, 2013
PRMT4 interacts with NCOA4 to inhibit ferritinophagy in cisplatin-induced acute kidney injury
Lizhi Zhou1,2, Zebin Deng1,2, Yilong Wang3
1Department of Urology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
Abstract:
Cisplatin-induced acute kidney injury (AKI) is commonly seen in the clinical practice, and ferroptosis, a type of non-apoptotic cell death, plays a pivotal role in it. Previous studies suggested that protein arginine methyltransferase 4 (PRMT4) was incorporated in various bioprocesses, but its role in renal injuries has not been investigated. Our present study 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 type of selective autophagy favoring lipid peroxidation to accelerate ferroptosis. Taken together, our study demonstrated that PRMT4 interacted with NCOA4 to attenuate ferroptosis in cisplatin-induced AKI, suggesting that PRMT4 might present as a new therapeutic target for cisplatin-related nephropathy.
Insights
Protein arginine methyltransferase 4 (PRMT4) protects against cisplatin-induced acute kidney injury (AKI) by inhibiting ferroptosis. Downregulation of PRMT4 worsens kidney damage, suggesting PRMT4 as a potential therapeutic target for nephropathy.
Area of Science:
- Nephrology
- Cell Death Mechanisms
- Molecular Biology
Background:
- Cisplatin chemotherapy can cause acute kidney injury (AKI), a serious clinical concern.
- Ferroptosis, a distinct form of cell death, is implicated in the pathogenesis of cisplatin-induced AKI.
- The role of protein arginine methyltransferase 4 (PRMT4) in kidney injury remains unexplored.
Purpose of the Study:
- To investigate the role of PRMT4 in cisplatin-induced AKI.
- To elucidate the underlying molecular mechanisms by which PRMT4 affects renal injury.
Main Methods:
- Assessed PRMT4 expression in renal proximal tubular cells.
- Utilized genetic disruption and overexpression of PRMT4 in models of cisplatin-induced AKI.
- Investigated the interaction between PRMT4 and NCOA4 and its effect on ferritinophagy and ferroptosis.
Main Results:
- PRMT4 expression was found to be high in renal proximal tubular cells but downregulated in cisplatin-induced AKI.
- Genetic deletion of PRMT4 aggravated cisplatin-induced kidney injury and redox damage.
- Overexpression of PRMT4 attenuated cisplatin-induced renal damage.
- PRMT4 was shown to interact with NCOA4, inhibiting ferritinophagy and subsequent ferroptosis.
Conclusions:
- PRMT4 plays a protective role in cisplatin-induced AKI by inhibiting ferroptosis through interaction with NCOA4.
- PRMT4 represents a potential therapeutic target for mitigating cisplatin-induced nephropathy.
