Journal Article Epublish 2 citations
PubMed: 38279224 DOI: 10.3390/ijms25021223
Tubular Endogenous Erythropoietin Protects Renal Function against Ischemic Reperfusion Injury.
Int J Mol Sci 25(2)
Authors: Yukiko Yasuoka, Yuichiro Izumi, Takashi Fukuyama, Tomomi Oshima, Taiga Yamazaki, Takayuki Uematsu, Noritada Kobayashi, Masayoshi Nanami, Yoshitaka Shimada, Yasushi Nagaba, Masashi Mukoyama, Jeff M Sands, Noriko Takahashi, Katsumasa Kawahara, Hiroshi Nonoguchi
Affiliations
- Department of Physiology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara 252-0374, Kanagawa, Japan.
- Department of Nephrology, Kumamoto University Graduate School of Medical Sciences, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, Kumamoto, Japan.
- Division of Biomedical Research, Kitasato University Medical Center, 6-100 Arai, Kitamoto 364-8501, Saitama, Japan.
- Division of Kidney and Dialysis, Department of Internal Medicine, Hyogo Medical University, 1-1 Mukogawa-cho, Nishinomiya 663-8501, Hyogo, Japan.
- Division of Internal Medicine, Kitasato University Medical Center, 6-100 Arai, Kitamoto 364-8501, Saitama, Japan.
- Renal Division, Department of Medicine, Emory University School of Medicine, 1639 Pierce Drive, WMB Room 3313, Atlanta, GA 30322, USA.
Abstract
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% O) 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.
MeSH
Erythropoietin, Cells, Reperfusion Injury