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The following is a summary of “Nur77 Promotes Inflammation in Cisplatin-Induced Acute Kidney Injury Through Transactivation of SERPINA3 Mediating Wnt/β-Catenin Pathway,” published in the February 2025 issue of Nephrology by Zhou et al.
Acute kidney injury (AKI) is a common complication of cisplatin treatment. Nur77 promotes renal ischemia–reperfusion injury.
Researchers conducted a retrospective study to examine Nur77’s role in cisplatin-induced AKI (CI-AKI) and its mechanism.
They treated HK-2 cells with cisplatin to model CI-AKI in vitro. They analyzed cell viability and proliferation using CCK-8 and EdU assays. They assessed apoptosis by flow cytometry and inflammation levels by ELISA. They evaluated molecular abundance using qPCR, Western blot, and immunofluorescence. They confirmed Nur77-SERPINA3 interaction using ChIP and dual-luciferase reporter assays.
The results showed that Nur77 and SERPINA3 expression increased in cisplatin-induced HK-2 cells. SERPINA3 silencing improved cell viability and proliferation while reducing apoptosis and inflammatory cytokine release. Nur77 bound to the SERPINA3 promoter (−182 to −175), upregulating SERPINA3 and activating Wnt/β-catenin. Nur77 knockdown significantly reduced cisplatin-induced HK-2 cell injury, but SERPINA3 overexpression counteracted this effect.
Investigators found that Nur77 knockdown reduced cisplatin-induced HK-2 cell injury by lowering SERPINA3 expression and inactivating the Wnt/β-catenin pathway.
Source: onlinelibrary.wiley.com/doi/abs/10.1111/nep.70006
