Tubular Endogenous Erythropoietin Protects Renal Function against Ischemic Reperfusion Injury
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- Yukiko Yasuoka
- Department of Physiology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara 252-0374, Kanagawa, Japan
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- Yuichiro Izumi
- Department of Nephrology, Kumamoto University Graduate School of Medical Sciences, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, Kumamoto, Japan
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- Takashi Fukuyama
- Division of Biomedical Research, Kitasato University Medical Center, 6-100 Arai, Kitamoto 364-8501, Saitama, Japan
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- Tomomi Oshima
- Department of Physiology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara 252-0374, Kanagawa, Japan
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- Taiga Yamazaki
- Division of Biomedical Research, Kitasato University Medical Center, 6-100 Arai, Kitamoto 364-8501, Saitama, Japan
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- Takayuki Uematsu
- Division of Biomedical Research, Kitasato University Medical Center, 6-100 Arai, Kitamoto 364-8501, Saitama, Japan
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- Noritada Kobayashi
- Division of Biomedical Research, Kitasato University Medical Center, 6-100 Arai, Kitamoto 364-8501, Saitama, Japan
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- Masayoshi Nanami
- Division of Kidney and Dialysis, Department of Internal Medicine, Hyogo Medical University, 1-1 Mukogawa-cho, Nishinomiya 663-8501, Hyogo, Japan
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- Yoshitaka Shimada
- Division of Internal Medicine, Kitasato University Medical Center, 6-100 Arai, Kitamoto 364-8501, Saitama, Japan
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- Yasushi Nagaba
- Division of Internal Medicine, Kitasato University Medical Center, 6-100 Arai, Kitamoto 364-8501, Saitama, Japan
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- Masashi Mukoyama
- Department of Nephrology, Kumamoto University Graduate School of Medical Sciences, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, Kumamoto, Japan
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- Jeff M. Sands
- Renal Division, Department of Medicine, Emory University School of Medicine, 1639 Pierce Drive, WMB Room 3313, Atlanta, GA 30322, USA
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- Noriko Takahashi
- Department of Physiology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara 252-0374, Kanagawa, Japan
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- Katsumasa Kawahara
- Department of Physiology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara 252-0374, Kanagawa, Japan
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- 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>
収録刊行物
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- International Journal of Molecular Sciences
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International Journal of Molecular Sciences 25 (2), 1223-, 2024-01-19
MDPI AG
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詳細情報 詳細情報について
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- CRID
- 1360302866852416256
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- ISSN
- 14220067
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- 資料種別
- journal article
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- データソース種別
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- Crossref
- KAKEN
- OpenAIRE