LCN2 attenuates sepsis-induced liver injury by alleviating PTGS2-mediated Ferroptosis

Abstract

Abstract Sepsis, which is strongly linked to sepsis-induced liver injury, is a significant contributor to mortality in critical care units. In this study, we explore the role of lipocalin 2 (LCN2) in sepsis-induced liver injury. We observed increased expression of LCN2 in the livers of septic mice induced by caecal ligation and puncture (CLP), as well as in hepatocytes treated with lipopolysaccharide (LPS). To elucidate the function of LCN2 in sepsis-induced liver injury, we established septic mice with LCN2 knockdown. To evaluate liver injury in mice, levels of alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP) were measured in both serum and liver samples. Oxidative stress was evaluated by measuring the levels of malondialdehyde (MDA) and the activities of superoxide dismutase (SOD) and glutathione (GSH) in serum and liver samples. Additionally, ferroptosis was assessed by examining the expression of Prostaglandin-Endoperoxide Synthase 2 (Ptgs2), solute carrier family 7 member 11 (Slc7a11) and glutathione peroxidase 4 (Gpx4) in the liver tissue of the mice. Our findings demonstrated that LCN2 knockdown significantly exacerbated sepsis-induced liver injury, oxidative stress, and ferroptosis. Moreover, in an in vitro study, LCN2 overexpression notably ameliorated LPS-induced liver injury, oxidative stress, and ferroptosis in hepatocytes by inhibiting PTGS2 expression. In conclusion, our study provides evidence that LCN2 attenuates sepsis-induced liver injury by alleviating PTGS2-mediated ferroptosis.