RIPK3 mediates renal tubular epithelial cell apoptosis in endotoxin‑induced acute kidney injury

Abstract

Renal tubular epithelial cell apoptosis is an important pathological mechanism of septic acute kidney injury (AKI). Endotoxin, also known as lipopolysaccharide (LPS), has a key role in septic AKI and can directly induce tubular epithelial cell apoptosis. The upregulation of receptor-interacting protein kinase 3 (RIPK3) in tubular epithelial cells has been reported in septic AKI, with RIPK3 mediating apoptosis in several cell types. In the present study, the effect of RIPK3 on endotoxin-induced AKI was investigated in mouse tubular epithelial cell apoptosis in vitro and in vivo. It was found that the expression of RIPK3 was markedly increased in endotoxin-induced AKI. Endotoxin-induced AKI and tubular epithelial cell apoptosis could be attenuated by GSK'872, a RIPK3 inhibitor. LPS stimulation also upregulated RIPK3 expression in tubular epithelial cells in a time-dependent manner. Both RIPK3 inhibitor and small interfering RNA (siRNA) targeting RIPK3 reduced LPS-induced tubular epithelial cell apoptosis in vitro. The expression of the proapoptotic protein Bax was induced by LPS and reversed by GSK'872 or RIPK3-siRNA. The present study revealed that RIPK3 mediated renal tubular cell apoptosis in endotoxin-induced AKI. RIPK3 may be a potential target for the prevention of renal tubular cell apoptosis in endotoxin-induced AKI.