CD36 promotes tubular ferroptosis by regulating the ubiquitination of FSP1 in acute kidney injury

作者全名："Ma, Yixin; Huang, Lili; Zhang, Zheng; Yang, Pengfei; Chen, Qingsong; Zeng, Xujia; Tan, Fangyan; Wang, Chunxia; Ruan, Xiongzhong; Liao, Xiaohui"

作者地址："[Ma, Yixin; Huang, Lili; Zhang, Zheng; Yang, Pengfei; Chen, Qingsong; Zeng, Xujia; Tan, Fangyan; Wang, Chunxia; Liao, Xiaohui] Chongqing Med Univ, Affiliated Hosp 2, Dept Nephrol, Chongqing 400010, Peoples R China; [Zhang, Zheng] Chongqing Med Univ, Dept Cell Biol & Genet, Chongqing 400016, Peoples R China; [Ruan, Xiongzhong] UCL, Royal Free & Univ Coll Med Sch, Ctr Nephrol, Royal Free Campus,Rowland Hill St, London NW3 2PF, England; [Ruan, Xiongzhong] Chongqing Med Univ, Ctr Lipid Res, Key Lab Mol Biol Infect Dis, Minist ofEducat, Chongqing 400016, Peoples R China; [Ruan, Xiongzhong; Liao, Xiaohui] Chongqing Med Univ, Ctr Lipid Res, Kuanren Lab Translat Lipidol, Affiliated Hosp 2, Chongqing 400010, Peoples R China"

通信作者："Liao, XH (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Dept Nephrol, Chongqing 400010, Peoples R China.; Liao, XH (通讯作者)，Chongqing Med Univ, Ctr Lipid Res, Kuanren Lab Translat Lipidol, Affiliated Hosp 2, Chongqing 400010, Peoples R China."

来源：GENES & DISEASES

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001052524000001

JCR分区：Q1

影响因子：6.8

年份：2024

卷号：11

期号：1

开始页：449

结束页：463

文献类型：Article

关键词：Acute kidney injury; CD36; Ferroptosis; FSP1; Ubiquitin-dependent degradation

摘要："Reactive oxidative species (ROS) production-driven ferroptosis plays a role in acute kidney injury (AKI). However, its exact molecular mechanism is poorly understood. Scavenger receptor CD36 has important roles in oxidizing lipids, lipid accumulation, metabolic syndrome, and insulin resistance in chronic kidney disease, but its roles remain unexplored in AKI. The present study investigated the role and mechanism of CD36 in regulating proximal tubular cell ferroptosis and AKI. The expression of CD36 was found to be significantly up-regulated in AKI renal tissues and correlated with renal function, which might serve as an independent biomarker for AKI patients. Moreover, in adult mice subjected to AKI, deletion of CD36 (CD36-/-) induced tubular cell ROS accumulation, ferroptosis activation, and renal injury. Mechanistically, combining LC-MS/MS, co-IP, and ubiquitination analyses revealed that CD36 could specifically bind to ferroptosis suppressor protein 1 (FSP1) and regulate its ubiquitination at sites K16 and K24, leading to FSP1 degradation and progression of ferroptosis in AKI. The present results emphasize a novel mechanism of CD36 in cisplatin-induced AKI. The discovery of the special CD36 roles in promoting ferroptosis and AKI development by regulating the ubi-quitinat ion of FSP1 in proximal tubular cells may be potential therapeutic targets for AKI. Moreover, CD36 may play a key role in the progression of AKI. Therefore, targeting CD36 may provide a promising treatment option for AKI. 2023 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons. org/licenses/by-nc-nd/4.0/)."

基金机构：National Natural Science Foundation of China [81873604]; Medical Scientific Research Project of the Chongqing Health Com- mission (China) [2022GDRC005]; Chongqing Science and Technology Agency (China) [CSTB2022NSCQ-MSX0984]

基金资助正文："Funding This work was supported by grants from the National Natural Science Foundation of China (No. 81873604) , the Medical Scientific Research Project of the Chongqing Health Com- mission (China) (No. 2022GDRC005) , and Chongqing Science and Technology Agency (China) (CSTB2022NSCQ-MSX0984) ."