Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Tubular Endogenous Erythropoietin Protects Renal Function against Ischemic Reperfusion Injury

Yukiko Yasuoka
ORCID logo ,
Yuichiro Izumi
ORCID logo ,
Takashi Fukuyama
,
Tomomi Oshima
,
Taiga Yamazaki
ORCID logo ,
Takayuki Uematsu
,
Noritada Kobayashi
,
Masayoshi Nanami
,
Yoshitaka Shimada
,
Yasushi Nagaba
,
Masashi Mukoyama
ORCID logo ,
Jeff M Sands
,
Noriko Takahashi
,
Katsumasa Kawahara
,
Hiroshi Nonoguchi
* ORCID logo
Version 1 : Received: 26 November 2023 / Approved: 27 November 2023 / Online: 27 November 2023 (08:44:10 CET)

A peer-reviewed article of this Preprint also exists.

Yasuoka, Y.; Izumi, Y.; Fukuyama, T.; Oshima, T.; Yamazaki, T.; Uematsu, T.; Kobayashi, N.; Nanami, M.; Shimada, Y.; Nagaba, Y.; Mukoyama, M.; Sands, J.M.; Takahashi, N.; Kawahara, K.; Nonoguchi, H. Tubular Endogenous Erythropoietin Protects Renal Function against Ischemic Reperfusion Injury. Int. J. Mol. Sci. 2024, 25, 1223. Yasuoka, Y.; Izumi, Y.; Fukuyama, T.; Oshima, T.; Yamazaki, T.; Uematsu, T.; Kobayashi, N.; Nanami, M.; Shimada, Y.; Nagaba, Y.; Mukoyama, M.; Sands, J.M.; Takahashi, N.; Kawahara, K.; Nonoguchi, H. Tubular Endogenous Erythropoietin Protects Renal Function against Ischemic Reperfusion Injury. Int. J. Mol. Sci. 2024, 25, 1223.

Abstract

Many large-scale studies revealed that exogenous erythropoietin, erythropoie-sis-stimulating agents, have no renoprotective effects. We investigated the effects of en-dogenous erythropoietin on renal function in ischemic reperfusion injury (IRI) of kidney using prolyl hydroxylase domaine (PHD) inhibitor, Roxadustat (ROX). 4 hr hypoxia (7% O2) and 4 hr treatment by ROX prior to IRI did not improve renal function. In contrast, 24-72 hr pre-treatment by ROX largely improved the decline of renal function by IRI. Hy-poxia and 4 hr ROX increased interstitial cells-derived Epo production by 75 and 6-fold, respectively, before IRI and worked as exogenous Epo. 24-72 hr ROX treatment increased Epo production during IRI by 9-fold. Immunohistochemistry revealed that 24 hr ROX caused Epo production in proximal and distal tubules and worked as endogenous Epo. Our data show that 24-72 hr ROX-induced tubular endogenous Epo production results in renoprotection but peritubular exogenous Epo production by interstitial cells-derived in-duced by hypoxia and 4 hr ROX did not. Stimulation of tubular but not peritubular Epo production may link to renoprotection.

Keywords

erythropoietin; PHD inhibitor; hypoxia; deglycosylation; proximal tubules; distal tubules; renal erythropoietin-producing interstitial cells

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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