【Background】
A systemic inflammatory response caused by sepsis leads to widespread organ dysfunction, including acute kidney injury. However, the pathogenetic mechanisms of acute kidney injury（AKI） in sepsis remain fully elucidated. Recently, it has been reported that plasminogen activator inhibitor-1 (PAI-1) which is induced by interleukin (IL)-6, plays a central role in thrombogenesis in septic patients. The aim of this study is to elucidate the involvement of PAI-1 in septic AKI using lipopolysaccharide (LPS)-induce AKI model.
【Methods/Results】
C57BL/6J mice were intraperitoneally treated with LPS. LPS administration elevated IL-6 expression in sera. Quantitative PCR demonstrated that the mRNA expression of Pai-1 was increased in kidneys 6 hours after LPS treatment. Administration of IL-6 to LPS model mice further increased PAI-1 expression compared to LPS alone, accompanied by renal impairment. Finally, to investigate whether PAI-1 is involved in kidney injury, TM5441, a PAI-1 inhibitor, was used. Administration of TM5441 suppressed urinary albumin/creatinine ratio, a kidney injury marker, and Lcn2 mRNA expression, a tubular injury marker.
【Conclusion】
PAI-1 induction, which is potentiated by IL-6, contributes to the pathogenesis of LPS-induced AKI.