2. Academic Validation
  3. A renal YY1-KIM1-DR5 axis regulates the progression of acute kidney injury

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

  • Nat Commun. 2023 Jul 17;14(1):4261. doi: 10.1038/s41467-023-40036-z.
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 5,  Kun Huang 6 7,  Ling Zheng 8
Affiliations

Affiliations

  • 1 School of Pharmacy, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Huazhong University of Science and Technology, Wuhan, 430030, China.
  • 2 Hubei Key Laboratory of Cell Homeostasis, Frontier Science Center for Immunology and Metabolism, College of Life Sciences, Wuhan University, Wuhan, 430072, China.
  • 3 Department of Pharmacy, The Third Hospital of Wuhan, Tongren Hospital of Wuhan University, Wuhan, 430070, China.
  • 4 Foundational Sciences, Central Michigan University College of Medicine, Mt. Pleasant, MI, 48859, USA.
  • 5 School of Pharmacy, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Huazhong University of Science and Technology, Wuhan, 430030, China. [email protected].
  • 6 School of Pharmacy, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Huazhong University of Science and Technology, Wuhan, 430030, China. [email protected].
  • 7 Tongji-RongCheng Biomedical Center, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. [email protected].
  • 8 Hubei Key Laboratory of Cell Homeostasis, Frontier Science Center for Immunology and Metabolism, College of Life Sciences, Wuhan University, Wuhan, 430072, China. [email protected].
  • # Contributed equally.
PMID: 37460623 DOI: 10.1038/s41467-023-40036-z
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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