PAI-1 induction is a critical event for the onset of lipopolysaccharide-induced acute kidney injury.

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  • Koki Tanaka
    Laboratory of Clinical Science and Biomedicine, Graduate School of Pharmaceutical sciences, Osaka University
  • Obana Masanori
    Laboratory of Clinical Science and Biomedicine, Graduate School of Pharmaceutical sciences, Osaka University Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives (OTRI), Osaka University
  • Sakai Hibiki
    Laboratory of Clinical Science and Biomedicine, Graduate School of Pharmaceutical sciences, Osaka University
  • Kamuro Hiroyasu
    Laboratory of Clinical Science and Biomedicine, Graduate School of Pharmaceutical sciences, Osaka University
  • Yamamoto Ayaha
    Laboratory of Clinical Science and Biomedicine, Graduate School of Pharmaceutical sciences, Osaka University
  • Tanaka Syota
    Laboratory of Clinical Science and Biomedicine, Graduate School of Pharmaceutical sciences, Osaka University
  • Okada Yoshiaki
    Laboratory of Clinical Science and Biomedicine, Graduate School of Pharmaceutical sciences, Osaka University
  • Fujio Yasushi
    Laboratory of Clinical Science and Biomedicine, Graduate School of Pharmaceutical sciences, Osaka University Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives (OTRI), Osaka University

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Other Title
  • PAI-1の発現誘導はlipopolysaccharideによる急性腎障害発症に重要である

Abstract

<p>【Background】</p><p>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.</p><p>【Methods/Results】</p><p>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.</p><p>【Conclusion】</p><p>PAI-1 induction, which is potentiated by IL-6, contributes to the pathogenesis of LPS-induced AKI.</p>

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