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A renal YY1-KIM1-DR5 axis regulates the progression of acute kidney injury

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收录情况： ◇ SCIE ◇ 自然指数

作者：
Chen Yang[1] * ; Huidie Xu[1] * ; Dong Yang[1,2] ; Yunhao Xie[2] ; Mingrui Xiong[1] ; Yu Fan[2] ; XiKai Liu[2] ; Yu Zhang[1] ; Yushuo Xiao[1] ; Yuchen Chen [1] ; Yihao Zhou[2] ; Liangliang Song[1] ; Chen Wang[1] ; Anlin Peng[3] ; Robert B. Petersen [4] ; Hong Chen [1] ; Kun Huang[1,5] ; Ling Zheng [2] ;
机构： [1]School of Pharmacy, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, HuazhongUniversity of Science and Technology, Wuhan 430030, China [2]Hubei Key Laboratory of Cell Homeostasis, Frontier Science Center for Immunology andMetabolism, College of Life Sciences, Wuhan University, Wuhan 430072, China [3]Department of Pharmacy, The Third Hospital of Wuhan, Tongren Hospital ofWuhan University, Wuhan 430070, China [4]Foundational Sciences, Central Michigan University College of Medicine, Mt.Pleasant, MI 48859, USA [5]TongjiRongCheng Biomedical Center, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
出处：
DOI： 10.1038/s41467-023-40036-z
ISSN：

摘要：
Acute kidney injury (AKI) exhibits high morbidity and mortality. Kidney injury molecule-1 (KIM1) is dramatically upregulated in renal tubules upon injury, and acts as a biomarker for various renal diseases. However, the exact role and underlying mechanism of KIM1 in the progression of AKI remain elusive. Herein, we report that renal tubular specific knockout of Kim1 attenuates cisplatin- or ischemia/reperfusion-induced AKI in male mice. Mechanistically, transcription factor Yin Yang 1 (YY1), which is downregulated upon AKI, binds to the promoter of KIM1 and represses its expression. Injury-induced KIM1 binds to the ECD domain of death receptor 5 (DR5), which activates DR5 and the following caspase cascade by promoting its multimerization, thus induces renal cell apoptosis and exacerbates AKI. Blocking the KIM1-DR5 interaction with rationally designed peptides exhibit reno-protective effects against AKI. Here, we reveal a YY1-KIM1-DR5 axis in the progression of AKI, which warrants future exploration as therapeutic targets.© 2023. The Author(s).

基金：
This work is supported by the National Key R&D Program of China (2022YFA0806100 to K.H.; 2018YFA0800700 and 2019YFA0802701 to L.Z.), the Natural Science Foundation of China (32021003 to L.Z.; 31971066 and 82273838 to K.H.), the Fundamental Research Funds for the Central Universities (2042022dx0003 to L.Z.), and the Natural Science Foundation of Hubei Province (2021CFA004 to K.H.; 2022CFB247 to H.C., and 2022DFE025 to A.P.).
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外文
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中科院(CAS)分区：
出版当年[2022]版：
大类 | 1 区 综合性期刊
小类 | 1 区 综合性期刊
最新[2023]版：
大类 | 1 区 综合性期刊
小类 | 1 区 综合性期刊
JCR分区：
出版当年[2021]版：
Q1 MULTIDISCIPLINARY SCIENCES
最新[2023]版：
Q1 MULTIDISCIPLINARY SCIENCES

影响因子： 最新[2023版] 最新五年平均 出版当年[2021版] 出版当年五年平均 出版前一年[2020版] 出版后一年[2022版]

第一作者：
第一作者机构： [1]School of Pharmacy, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, HuazhongUniversity of Science and Technology, Wuhan 430030, China
共同第一作者：
通讯作者：
通讯机构： [1]School of Pharmacy, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, HuazhongUniversity of Science and Technology, Wuhan 430030, China [5]TongjiRongCheng Biomedical Center, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
推荐引用方式(GB/T 7714)：
Chen Yang,Huidie Xu,Dong Yang,et al.A renal YY1-KIM1-DR5 axis regulates the progression of acute kidney injury[J].NATURE COMMUNICATIONS.2023,14(1):doi:10.1038/s41467-023-40036-z.
APA：
Chen Yang,Huidie Xu,Dong Yang,Yunhao Xie,Mingrui Xiong...&Ling Zheng.(2023).A renal YY1-KIM1-DR5 axis regulates the progression of acute kidney injury.NATURE COMMUNICATIONS,14,(1)
MLA：
Chen Yang,et al."A renal YY1-KIM1-DR5 axis regulates the progression of acute kidney injury".NATURE COMMUNICATIONS 14..1(2023)

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