부산대학교 도서관

Introduction Acute kidney injury (AKI) is a clinical syndrome characterized by the rapid loss of kidney function and abrupt kidney damage. Septic AKI is the most common complication of sepsis, [...]
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. Key words: endotoxin, acute kidney injury, renal tubular epithelial cell, apoptosis, receptor-interacting protein kinase 3