Increased OASIS in podocytes contributes to the disruption of kidney homeostasis

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  • Miyake Yoshiaki
    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 Global Center for Medical Engineering and Informatics (MEI), Osaka University Radioisotope Research Center, Institute for Radiation Sciences, Osaka University
  • Yamamoto Ayaha
    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
  • Maeda Makiko
    Laboratory of Clinical Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University
  • Okada Yoshiaki
    Laboratory of Clinical Science and Biomedicine, Graduate School of Pharmaceutical Sciences, Osaka University
  • Imaizumi Kazunori
    Department of Biochemistry, Institute of Biomedical & Health Sciences, Hiroshima University
  • Asanuma Katsuhiko
    Department of Nephrology, Graduate School of Medicine, Chiba 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
  • ポドサイトにおける転写因子OASISの発現増加は腎臓の恒常性破綻をもたらす

Abstract

<p>[Background]</p><p>Podocytes, a component of glomerular filtration barrier, are damaged under various stresses in kidney diseases. Previously, we revealed that a transcription factor old astrocyte specifically induced substance (OASIS) in kidney myofibroblasts promoted kidney fibrosis. However, the role of OASIS in podocytes remains unclear. </p><p>[Methods/Results]</p><p>LPS treatment increased OASIS expression in podocytes. To examine the roles of OASIS in podocytes, we generated podocyte-specific OASIS knockout (cKO) mice. Podocyte-specific OASIS deletion suppressed LPS-increased serum creatinine level, but did not influence albuminuria and podocyte injury. Interestingly, on the other hand, OASIS cKO mice were protected from LPS-mediated tubular injury. Microarray analysis using OASIS-overexpressed podocytes revealed that PRKCI was negatively regulated by OASIS in podocytes. We also found that recombinant PRKCI suppressed LPS-induced tubular injury in HK-2 cells in a dose-dependent manner. Finally, we established podocyte-restricted OASIS overexpressing transgenic mice and revealed that OASIS overexpression in podocytes caused tubular injury and kidney fibrosis, concomitant with severe albuminuria and podocyte foot process effacement.</p><p>[Conclusion]</p><p>Upregulation of OASIS in podocytes disturbs kidney homeostasis, leading to renal dysfunction.</p>

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