Erythropoietin modulates macrophages but not post-ischemic acute kidney injury in mice
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 erythropo...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2019-01-01
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| Series: | Journal of the Formosan Medical Association |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0929664618305060 |
| _version_ | 1818216668084568064 |
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| author | Yu-Hsiang Chou Fang-Ling Liao Yi-Ting Chen Pei-Ying Yeh Chia-Hao Liu Hong-Mou Shih Fan-Chi Chang Wen-Chih Chiang Tzong-Shinn Chu Shuei-Liong Lin |
| author_facet | Yu-Hsiang Chou Fang-Ling Liao Yi-Ting Chen Pei-Ying Yeh Chia-Hao Liu Hong-Mou Shih Fan-Chi Chang Wen-Chih Chiang Tzong-Shinn Chu Shuei-Liong Lin |
| author_sort | Yu-Hsiang Chou |
| collection | DOAJ |
| description | 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. Keywords: Acute kidney injury, Colony-stimulating factor 2 receptor β, Erythropoietin, Ischemia-reperfusion injury, Macrophage |
| first_indexed | 2024-12-12T06:55:37Z |
| format | Article |
| id | doaj.art-2deeac55e64e4c958ec8bd8d024bcd9c |
| institution | Directory Open Access Journal |
| issn | 0929-6646 |
| language | English |
| last_indexed | 2024-12-12T06:55:37Z |
| publishDate | 2019-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of the Formosan Medical Association |
| spelling | doaj.art-2deeac55e64e4c958ec8bd8d024bcd9c2022-12-22T00:33:57ZengElsevierJournal of the Formosan Medical Association0929-66462019-01-011181494503Erythropoietin modulates macrophages but not post-ischemic acute kidney injury in miceYu-Hsiang Chou0Fang-Ling Liao1Yi-Ting Chen2Pei-Ying Yeh3Chia-Hao Liu4Hong-Mou Shih5Fan-Chi Chang6Wen-Chih Chiang7Tzong-Shinn Chu8Shuei-Liong Lin9Renal Division, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University Hospital Jin-Shan Branch, New Taipei City, Taiwan; Graduate Institute of Physiology, College of Medicine, National Taiwan University, Taipei, TaiwanGraduate Institute of Physiology, College of Medicine, National Taiwan University, Taipei, TaiwanRenal Division, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Physiology, College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Integrated Diagnostics &Therapeutics, National Taiwan University Hospital, Taipei, Taiwan; Department of Internal Medicine, E-DA Hospital, Kaohsiung, TaiwanGraduate Institute of Physiology, College of Medicine, National Taiwan University, Taipei, TaiwanGraduate Institute of Physiology, College of Medicine, National Taiwan University, Taipei, TaiwanGraduate Institute of Physiology, College of Medicine, National Taiwan University, Taipei, Taiwan; Division of Nephrology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, TaiwanRenal Division, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Physiology, College of Medicine, National Taiwan University, Taipei, TaiwanRenal Division, Department of Internal Medicine, National Taiwan University Hospital, Taipei, TaiwanRenal Division, Department of Internal Medicine, National Taiwan University Hospital, Taipei, TaiwanRenal Division, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Physiology, College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Integrated Diagnostics &Therapeutics, National Taiwan University Hospital, Taipei, Taiwan; Research Center for Developmental Biology and Regenerative Medicine, National Taiwan University, Taipei, Taiwan; Corresponding author. Graduate Institute of Physiology, No. 1, Jen-Ai Road Section 1, Taipei, 100, Taiwan.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. Keywords: Acute kidney injury, Colony-stimulating factor 2 receptor β, Erythropoietin, Ischemia-reperfusion injury, Macrophagehttp://www.sciencedirect.com/science/article/pii/S0929664618305060 |
| spellingShingle | Yu-Hsiang Chou Fang-Ling Liao Yi-Ting Chen Pei-Ying Yeh Chia-Hao Liu Hong-Mou Shih Fan-Chi Chang Wen-Chih Chiang Tzong-Shinn Chu Shuei-Liong Lin Erythropoietin modulates macrophages but not post-ischemic acute kidney injury in mice Journal of the Formosan Medical Association |
| title | Erythropoietin modulates macrophages but not post-ischemic acute kidney injury in mice |
| title_full | Erythropoietin modulates macrophages but not post-ischemic acute kidney injury in mice |
| title_fullStr | Erythropoietin modulates macrophages but not post-ischemic acute kidney injury in mice |
| title_full_unstemmed | Erythropoietin modulates macrophages but not post-ischemic acute kidney injury in mice |
| title_short | Erythropoietin modulates macrophages but not post-ischemic acute kidney injury in mice |
| title_sort | erythropoietin modulates macrophages but not post ischemic acute kidney injury in mice |
| url | http://www.sciencedirect.com/science/article/pii/S0929664618305060 |
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