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CIRBP promotes ferroptosis by interacting with ELAVL1 and activating ferritinophagy during renal ischaemia-reperfusion injury |
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| Authors: | Mingxing Sui Da Xu Wenyu Zhao Hanlan Lu Rui Chen Yazhe Duan Yanhua Li Youhua Zhu Lei Zhang Li Zeng |
| Institution: | 1. Department of Organ Transplantation, Shanghai Changhai Hospital, Shanghai, China
Contribution: Data curation (equal), Formal analysis (equal), Funding acquisition (equal), Investigation (equal), Methodology (equal), Resources (equal), Writing - original draft (equal), Writing - review & editing (equal);2. Department of Urology, The Third Affiliated Hospital of Naval Medical University, Shanghai, China Contribution: Data curation (equal), Investigation (equal), Methodology (equal), Resources (supporting), Software (supporting), Writing - original draft (equal), Writing - review & editing (equal);3. Department of Organ Transplantation, Shanghai Changhai Hospital, Shanghai, China Contribution: Investigation (equal), Methodology (equal), Project administration (supporting), Resources (supporting), Software (equal), Writing - review & editing (supporting);4. Department of Organ Transplantation, Shanghai Changhai Hospital, Shanghai, China Contribution: Methodology (supporting), Project administration (supporting), Resources (equal), Software (supporting);5. Department of Organ Transplantation, Shanghai Changhai Hospital, Shanghai, China Contribution: Project administration (supporting), Resources (equal), Software (supporting);6. Department of Organ Transplantation, Shanghai Changhai Hospital, Shanghai, China Contribution: Methodology (supporting), Project administration (supporting), Resources (supporting), Software (supporting);7. Department of Organ Transplantation, Shanghai Changhai Hospital, Shanghai, China Contribution: Investigation (supporting), Methodology (supporting), Project administration (supporting), Software (supporting), Validation (supporting);8. Department of Organ Transplantation, Shanghai Changhai Hospital, Shanghai, China The Committee of Experts of China Organ Donation, Beijing, China Contribution: Formal analysis (supporting), Investigation (supporting), Methodology (supporting), Resources (supporting);9. Department of Organ Transplantation, Shanghai Changhai Hospital, Shanghai, China |
| Abstract: | Renal ischaemia-reperfusion (IR) is a major cause of acute kidney injury (AKI). Cold-inducible RNA-binding protein (CIRBP) may contribute to AKI because its deficiency protects against renal IR injury in a mechanism believed to involve ferroptosis. We aimed to investigate whether ferroptosis is associated with CIRBP-mediated renal damage. The differential expression of CIRBP was examined in tubular epithelial (HK2) cells during hypoxia-reoxygenation (HR) or in response to erastin, an inducer of ferroptosis. CIRBP expression was increased in response to HR or erastin in HK2 cells but the silencing of CIRBP inhibited HR and erastin-induced ferroptosis together with ferritinophagy. We discovered an interaction between CIRBP and ELAVL1 using STRING software, which was verified through co-immunoprecipitation and fluorescence colocalization assays. We found that ELAVL1 is a critical regulator in the activation of ferritinophagy and the promotion of ferroptosis. HR or erastin also induced the expression of ELAVL1. An autophagy inhibitor (hydroxychloroquine) or si-ELAVL1 transfection reversed CIRBP-enhanced ferritinophagy activation and ferroptosis in HK2 cells under HR. Injection of anti-CIRBP antibody into a mouse model of IR inhibited ferroptosis and decreased renal IR injury in vivo. In summary, our results provide evidence that ferritinophagy-mediated ferroptosis could be responsible for CIRBP-enhanced renal IR injury. |
| Keywords: | acute kidney injury CIRBP ELAVL1 ferritinophagy ferroptosis ischaemia-reperfusion |