Tubular Endogenous Erythropoietin Protects Renal Function against Ischemic Reperfusion Injury

DOI DOI Web Site 参考文献55件 オープンアクセス
  • Yukiko Yasuoka
    Department of Physiology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara 252-0374, Kanagawa, Japan
  • Yuichiro Izumi
    Department of Nephrology, Kumamoto University Graduate School of Medical Sciences, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, Kumamoto, Japan
  • Takashi Fukuyama
    Division of Biomedical Research, Kitasato University Medical Center, 6-100 Arai, Kitamoto 364-8501, Saitama, Japan
  • Tomomi Oshima
    Department of Physiology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara 252-0374, Kanagawa, Japan
  • Taiga Yamazaki
    Division of Biomedical Research, Kitasato University Medical Center, 6-100 Arai, Kitamoto 364-8501, Saitama, Japan
  • Takayuki Uematsu
    Division of Biomedical Research, Kitasato University Medical Center, 6-100 Arai, Kitamoto 364-8501, Saitama, Japan
  • Noritada Kobayashi
    Division of Biomedical Research, Kitasato University Medical Center, 6-100 Arai, Kitamoto 364-8501, Saitama, Japan
  • Masayoshi Nanami
    Division of Kidney and Dialysis, Department of Internal Medicine, Hyogo Medical University, 1-1 Mukogawa-cho, Nishinomiya 663-8501, Hyogo, Japan
  • Yoshitaka Shimada
    Division of Internal Medicine, Kitasato University Medical Center, 6-100 Arai, Kitamoto 364-8501, Saitama, Japan
  • Yasushi Nagaba
    Division of Internal Medicine, Kitasato University Medical Center, 6-100 Arai, Kitamoto 364-8501, Saitama, Japan
  • Masashi Mukoyama
    Department of Nephrology, Kumamoto University Graduate School of Medical Sciences, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, Kumamoto, Japan
  • Jeff M. Sands
    Renal Division, Department of Medicine, Emory University School of Medicine, 1639 Pierce Drive, WMB Room 3313, Atlanta, GA 30322, USA
  • Noriko Takahashi
    Department of Physiology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara 252-0374, Kanagawa, Japan
  • Katsumasa Kawahara
    Department of Physiology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara 252-0374, Kanagawa, Japan
  • Hiroshi Nonoguchi
    Division of Internal Medicine, Kitasato University Medical Center, 6-100 Arai, Kitamoto 364-8501, Saitama, Japan

説明

<jats:p>Many large-scale studies show that exogenous erythropoietin, erythropoiesis-stimulating agents, lack any renoprotective effects. We investigated the effects of endogenous erythropoietin on renal function in kidney ischemic reperfusion injury (IRI) using the prolyl hydroxylase domain (PHD) inhibitor, Roxadustat (ROX). Four h of hypoxia (7% O2) and 4 h treatment by ROX prior to IRI did not improve renal function. In contrast, 24–72 h pretreatment by ROX significantly improved the decline of renal function caused by IRI. Hypoxia and 4 h ROX increased interstitial cells-derived Epo production by 75- and 6-fold, respectively, before IRI, and worked similarly to exogenous Epo. ROX treatment for 24–72 h increased Epo production during IRI by 9-fold. Immunohistochemistry revealed that 24 h ROX treatment induced Epo production in proximal and distal tubules and worked similarly to endogenous Epo. Our data show that tubular endogenous Epo production induced by 24–72 h ROX treatment results in renoprotection but peritubular exogenous Epo production by interstitial cells induced by hypoxia and 4 h ROX treatment did not. Stimulation of tubular, but not peritubular, Epo production may link to renoprotection.</jats:p>

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