TY - JOUR
T1 - A renal YY1-KIM1-DR5 axis regulates the progression of acute kidney injury
AU - Yang, Chen
AU - Xu, Huidie
AU - Yang, Dong
AU - Xie, Yunhao
AU - Xiong, Mingrui
AU - Fan, Yu
AU - Liu, Xi Kai
AU - Zhang, Yu
AU - Xiao, Yushuo
AU - Chen, Yuchen
AU - Zhou, Yihao
AU - Song, Liangliang
AU - Wang, Chen
AU - Peng, Anlin
AU - Petersen, Robert B.
AU - Chen, Hong
AU - Huang, Kun
AU - Zheng, Ling
N1 - Funding Information:
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.). The work was technically supported by the Analytical and Testing Center of Huazhong University of Science and Technology.
Publisher Copyright:
© 2023, The Author(s).
PY - 2023/12
Y1 - 2023/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85165032948&partnerID=8YFLogxK
U2 - 10.1038/s41467-023-40036-z
DO - 10.1038/s41467-023-40036-z
M3 - Article
C2 - 37460623
AN - SCOPUS:85165032948
SN - 2041-1723
VL - 14
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 4261
ER -