Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed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

Download PDF

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our Diversity statement.

Leave a public comment
Send a private comment to the author(s)
* All users must log in before leaving a comment
Views 0
Downloads 0
Comments 0
Metrics 0
Get PDF Cite Share 0
Bookmark BibSonomy Mendeley Reddit Delicious
×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.