A Renal YY1-KIM1-DR5 Axis Regulates the Progression of Acute Kidney Injury

Overview

Journal Nat Commun

Specialty Biology

Date 2023 Jul 17

PMID 37460623

Authors

Chen Yang

Huidie Xu

Dong Yang

Yunhao Xie

Mingrui Xiong

Yu Fan

Xikai Liu

Yu Zhang

Yushuo Xiao

Yuchen Chen

Yihao Zhou

Liangliang Song

Chen Wang

Anlin Peng

Robert B Petersen

Hong Chen

Kun Huang

Ling Zheng

Affiliations

Soon will be listed here.

Abstract

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.

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