A renal YY1-KIM1-DR5 axis regulates the progression of acute kidney injury.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 37460623.
- Also identified by DOI 10.1038/s41467-023-40036-z and PMC identifier 10352345.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- Acute Kidney Injury
- Kidney