Targeting STEAP4 ameliorates pericytes loss and vascular dysfunction in cisplatin induced mouse acute kidney injury - PubMed
4 hours ago
- #AKI
- #Cisplatin
- #STEAP4
- Cisplatin-induced nephrotoxicity lacks effective treatments, with vascular dysfunction being an early response.
- Cisplatin administration leads to increased renal vascular permeability and rapid loss of perivascular pericytes.
- In vitro, cisplatin accelerates cell death in primary human kidney microvascular pericytes (HKMPs).
- RNA-sequencing and proteomics show downregulation of STEAP4 in HKMPs post-cisplatin exposure.
- Reduced STEAP4 expression causes iron accumulation and lipid peroxidation, leading to ferroptosis in HKMPs.
- Overexpression of STEAP4 protects against cisplatin-induced pericyte injury.
- AAV9-STEAP4 delivery via renal artery increases STEAP4 expression, reduces pericyte loss, and attenuates vascular leakage.
- AAV9-STEAP4 treatment significantly decreases kidney injury compared to controls.
- Targeting STEAP4 presents a novel therapeutic strategy for cisplatin-induced acute kidney injury (AKI).