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

Chen Yang, Huidie Xu, Dong Yang, Yunhao Xie, Mingrui Xiong, Yu Fan, Xi Kai Liu, Yu Zhang, Yushuo Xiao, Yuchen Chen, Yihao Zhou, Liangliang Song, Chen Wang, Anlin Peng, Robert B. Petersen, Hong Chen, Kun Huang, Ling Zheng

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Article number4261
JournalNature Communications
Issue number1
StatePublished - Dec 2023


Dive into the research topics of 'A renal YY1-KIM1-DR5 axis regulates the progression of acute kidney injury'. Together they form a unique fingerprint.

Cite this