IL-6 family cytokines, STAT3 activators, exhibit differential effects in a ligand-specific manner in podocytes

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  • Sayuri Mitsuoka
    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
  • Miyake Yoshiaki
    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 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
  • 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
  • IL-6ファミリーサイトカインは、ポドサイトにおいて共通してSTAT3を活性化させるが、リガンド特異的な作用を示す

Abstract

<p>[Background] </p><p>IL-6 family cytokines play protective roles in cardiomyocytes via STAT3 activation. Glomerular podocytes, as an important component of the kidney blood filtration, are terminally differentiated cells as well as cardiomyocytes. Although some studies have shown that STAT3 activation is associated with podocyte dysfunction, it remains unclear whether activated STAT3 exhibits differential functions depending on cytokines. The aim of this study is to assess the effects of IL-6 family cytokines/STAT3 signaling in podocytes. </p><p>[Methods and results] </p><p>To examine the pathophysiological relevance of IL-6 family cytokines in kidney diseases, C57BL/6J mice were subjected to ischemia-reperfusion or lipopolysaccharide (LPS) treatment. Quantitative PCR demonstrated that the expression level of IL-6, leukemia inhibitory factor (LIF) and IL-11 was upregulated in injured kidneys. In cultured podocytes, STAT3 was rapidly activated in response to the stimulation with IL-6, LIF or IL-11. Interestingly, LIF and IL-11 treatment suppressed H2O2-induced cell death in cultured podocytes, whereas IL-6 tended to increase cell death. </p><p>[Conclusion]</p><p>STAT3 could differentially function in an activator cytokine-specific manner, in podocytes, providing the important information for the development of therapy targeting STAT3 for kidney diseases.</p>

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