Loss of nephric augmenter of liver regeneration facilitates acute kidney injury via ACSL4-mediated ferroptosis

作者全名："Huang, Lili; Zhang, Ling; Zhang, Zheng; Tan, Fangyan; Ma, Yixin; Zeng, Xujia; Cao, Dan; Deng, Lili; Liu, Qi; Sun, Hang; Shen, Bingbing; Liao, Xiaohui"

作者地址："[Huang, Lili; Zhang, Ling; Zhang, Zheng; Tan, Fangyan; Ma, Yixin; Zeng, Xujia; Cao, Dan; Deng, Lili; Liao, Xiaohui] Chongqing Med Univ, Affiliated Hosp 2, Dept Nephrol, Chongqing, Peoples R China; [Zhang, Zheng] Chongqing Med Univ, Dept Cell Biol & Genet, Chongqing, Peoples R China; [Liu, Qi; Sun, Hang] Chongqing Med Univ, Inst Viral Hepatitis, Minist Educ, Key Lab Mol Biol Infect Dis,Affiliated Hosp 2, Chongqing, Peoples R China; [Shen, Bingbing] Chongqing Univ, Chongqing Emergency Med Ctr, Dept Nephrol, Cent Hosp, Chongqing, Peoples R China; [Liao, Xiaohui] Chongqing Med Univ, Ctr Lipid Res, Kuanren Lab Translat Lipidol, Affiliated Hosp 2, Chongqing, Peoples R China; [Liao, Xiaohui] Chongqing Med Univ, Affiliated Hosp 2, Dept Nephrol, 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."

来源：JOURNAL OF CELLULAR AND MOLECULAR MEDICINE

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001125145700001

JCR分区：Q2

影响因子：5.3

年份：2023

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：acute kidney injury; augmenter of liver regeneration; ferroptosis; lipid peroxidation; long-chain-fatty-acid-CoA ligase 4

摘要："Ferroptosis, characterized by lipid accumulation in intracellular compartments, is related to acute kidney injury (AKI), but the mechanism remains obscure. In our previous study, the protective effect of augmenter of liver regeneration (ALR) on AKI was not fully clarified. In this study, we established an AKI mouse model by knocking out proximal tubule-specific ALR and an AKI cell model by inducing hypoxia, as well as enrolled AKI patients, to investigate the effects of ALR on ferroptosis and the progression of AKI. We found that ALR knockout aggravated ferroptosis and increased ROS accumulation and mitochondrial damage, whereas ALR overexpression attenuated ferroptosis through clearance of ROS and maintenance of mitochondrial morphology. Mechanistically, we demonstrated that ALR could directly bind to long-chain-fatty-acid-CoA ligase 4 (ACSL4) and further inhibit the expression of ACSL4 by interacting with certain regions. By resolution liquid chromatography coupled with triple quadruple mass spectrometry, we found that ALR could reduce the contents of polyunsaturated fatty acids, especially arachidonic acid. In addition, we showed that ALR binds to ACSL4 and attenuates oxylipin accumulation, exerting a protective effect against ferroptosis in AKI. Therefore, targeting renal ALR can attenuate ferroptosis and can offer a promising strategy for the treatment of AKI."

基金机构：CQMU Program for Youth lnnovation in Future Medicine (W0173) and Chongqing Key Laboratory of Emergency Medicine Open Project

基金资助正文：No Statement Availabler No Statement Availabler No Statement Availabler No Statement Available