Erythropoietin modulates macrophages but not post-ischemic acute kidney injury in mice
Copyright © 2018 Formosan Medical Association. Published by Elsevier B.V. All rights reserved..
BACKGROUND/PURPOSE: Substantial progress was made in acute kidney injury (AKI) over the past 10 years, but no therapeutic interventions have been shown to prevent AKI or accelerate functional recovery after injury. A large number of preclinical studies supports the use of recombinant human erythropoietin (rHuEPO) to prevent AKI, but the clinical trial data are inconclusive. To address concerns about preclinical study design and reporting in AKI, we here presented our rigorous experiments on the use of rHuEPO in a mouse model simulating the most common post-ischemic AKI in patients.
METHODS: Use of saline vehicle or rHuEPO (100 or 1000 U/KgBW) in mice subjected to AKI induced by ischemia-reperfusion injury of left kidney 2 weeks after right nephrectomy (NX + IRI).
RESULTS: NX + IRI resulted in a reproducible AKI model. Use of rHuEPO as a pretreatment or posttreatment did not affect AKI severity, functional recovery, and mouse survival regardless of gender, injury severity, or doses of rHuEPO. Administering rHuEPO with 1000 U/KgBW did increase hematocrit and modulate AKI kidney macrophages by Nos2 downregulation and Ccl17 upregulation. Active expression of erythropoietin receptor (EPOR) was not identified in renal cells by lineage tracing study, whereas expression of colony-stimulating factor 2 receptor β (CSF2Rβ) was identified in kidney macrophages and upregulated after AKI. Both EPOR and CSF2Rβ were identified in cultured bone marrow derived macrophages, possibly mediated the robust inhibition of cytokine-induced phenotype switching by rHuEPO.
CONCLUSION: Use of rHuEPO can modulate macrophage function but not the post-ischemic AKI severity, functional recovery and survival in mice.
Medienart: |
E-Artikel |
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Erscheinungsjahr: |
2019 |
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Erschienen: |
2019 |
Enthalten in: |
Zur Gesamtaufnahme - volume:118 |
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Enthalten in: |
Journal of the Formosan Medical Association = Taiwan yi zhi - 118(2019), 1 Pt 3 vom: 29. Jan., Seite 494-503 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Chou, Yu-Hsiang [VerfasserIn] |
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Links: |
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Themen: |
11096-26-7 |
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Anmerkungen: |
Date Completed 12.03.2019 Date Revised 12.03.2019 published: Print-Electronic Citation Status MEDLINE |
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doi: |
10.1016/j.jfma.2018.10.015 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM290474620 |
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520 | |a Copyright © 2018 Formosan Medical Association. Published by Elsevier B.V. All rights reserved. | ||
520 | |a BACKGROUND/PURPOSE: Substantial progress was made in acute kidney injury (AKI) over the past 10 years, but no therapeutic interventions have been shown to prevent AKI or accelerate functional recovery after injury. A large number of preclinical studies supports the use of recombinant human erythropoietin (rHuEPO) to prevent AKI, but the clinical trial data are inconclusive. To address concerns about preclinical study design and reporting in AKI, we here presented our rigorous experiments on the use of rHuEPO in a mouse model simulating the most common post-ischemic AKI in patients | ||
520 | |a METHODS: Use of saline vehicle or rHuEPO (100 or 1000 U/KgBW) in mice subjected to AKI induced by ischemia-reperfusion injury of left kidney 2 weeks after right nephrectomy (NX + IRI) | ||
520 | |a RESULTS: NX + IRI resulted in a reproducible AKI model. Use of rHuEPO as a pretreatment or posttreatment did not affect AKI severity, functional recovery, and mouse survival regardless of gender, injury severity, or doses of rHuEPO. Administering rHuEPO with 1000 U/KgBW did increase hematocrit and modulate AKI kidney macrophages by Nos2 downregulation and Ccl17 upregulation. Active expression of erythropoietin receptor (EPOR) was not identified in renal cells by lineage tracing study, whereas expression of colony-stimulating factor 2 receptor β (CSF2Rβ) was identified in kidney macrophages and upregulated after AKI. Both EPOR and CSF2Rβ were identified in cultured bone marrow derived macrophages, possibly mediated the robust inhibition of cytokine-induced phenotype switching by rHuEPO | ||
520 | |a CONCLUSION: Use of rHuEPO can modulate macrophage function but not the post-ischemic AKI severity, functional recovery and survival in mice | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Acute kidney injury | |
650 | 4 | |a Colony-stimulating factor 2 receptor β | |
650 | 4 | |a Erythropoietin | |
650 | 4 | |a Ischemia-reperfusion injury | |
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700 | 1 | |a Chen, Yi-Ting |e verfasserin |4 aut | |
700 | 1 | |a Yeh, Pei-Ying |e verfasserin |4 aut | |
700 | 1 | |a Liu, Chia-Hao |e verfasserin |4 aut | |
700 | 1 | |a Shih, Hong-Mou |e verfasserin |4 aut | |
700 | 1 | |a Chang, Fan-Chi |e verfasserin |4 aut | |
700 | 1 | |a Chiang, Wen-Chih |e verfasserin |4 aut | |
700 | 1 | |a Chu, Tzong-Shinn |e verfasserin |4 aut | |
700 | 1 | |a Lin, Shuei-Liong |e verfasserin |4 aut | |
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