Arid5a/IL-6/PAI-1 Signaling Is Involved in the Pathogenesis of Lipopolysaccharide-Induced Kidney Injury

DOI Web Site PubMed 参考文献29件
  • Tanaka Koki
    Laboratory of Clinical Science and Biomedicine, Graduate School of Pharmaceutical Sciences, Osaka University
  • Harada Hiroki
    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
  • Sakai Hibiki
    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
  • Tomimatsu Masashi
    Laboratory of Clinical Science and Biomedicine, Graduate School of Pharmaceutical Sciences, Osaka University
  • Ikeda Akari
    Laboratory of Clinical Science and Biomedicine, Graduate School of Pharmaceutical Sciences, Osaka University
  • Chosokabe Renya
    Laboratory of Clinical Science and Biomedicine, Graduate School of Pharmaceutical Sciences, Osaka University
  • Tanaka Shota
    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 Center for Infectious Disease Education and Research (CiDER), Osaka University
  • Fujio Yasushi
    Laboratory of Clinical Science and Biomedicine, Graduate School of Pharmaceutical Sciences, Osaka University Center for Infectious Disease Education and Research (CiDER), Osaka University Institute for Open and Transdisciplinary Research Initiatives (OTRI), Osaka University
  • Obana Masanori
    Laboratory of Clinical Science and Biomedicine, Graduate School of Pharmaceutical Sciences, Osaka University Center for Infectious Disease Education and Research (CiDER), Osaka University Institute for Open and Transdisciplinary Research Initiatives (OTRI), Osaka University Global Center for Medical Engineering and Informatics (MEI), Osaka University Radioisotope Research Center, Institute for Radiation Sciences, Osaka University

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<p>A systemic inflammatory response leads to widespread organ dysfunction, such as kidney dysfunction. Plasminogen activator inhibitor-1 (PAI-1) is involved in the pathogenesis of inflammatory kidney injury; however, the regulatory mechanism of PAI-1 in injured kidneys remains unclear. PAI-1 is induced by interleukin (IL)-6 in patients with sepsis. In addition, the stabilization of IL-6 is regulated by the adenine–thymine-rich interactive domain-containing protein 5a (Arid5a). Therefore, the aim of the present study was to examine the involvement of Arid5a/IL-6/PAI-1 signaling in lipopolysaccharide (LPS)-induced inflammatory kidney injury. LPS treatment to C57BL/6J mice upregulated Pai-1 mRNA in the kidneys. Enzyme-linked immunosorbent assay (ELISA) revealed that PAI-1 expression was induced in the culture supernatants of LPS-treated human umbilical vein endothelial cells, but not in those of LPS-treated human kidney 2 (HK-2) cells, a tubular cell line. Combined with single-cell analysis, endothelial cells were found to be responsible for PAI-1 elevation in LPS-treated kidneys. Administration of TM5441, a PAI-1 inhibitor, reduced the urinary albumin/creatinine ratio, concomitant with downregulation of Il-6 and Arid5a mRNA expressions. IL-6 treatment in LPS model mice further upregulated Pai-1 mRNA expression compared with LPS alone, accompanied by renal impairment. Furthermore, the expression of Il-6 and Pai-1 mRNA was lower in Arid5a knockout mice than in wild-type mice after LPS treatment. Taken together, the vicious cycle of Arid5a/IL-6/PAI-1 signaling is involved in LPS-induced kidney injury.</p>

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