Effects of orally active hypoxia inducible factor alpha prolyl hydroxylase inhibitor, FG4592 on renal fibrogenic potential in mouse unilateral ureteral obstruction model
Copyright © 2019 The Authors. Production and hosting by Elsevier B.V. All rights reserved..
Orally active hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitors that stabilize HIF protein and stimulate the production of erythropoietin have been approved to treat renal anemia. Our previous report suggested that HIF-1α dependent fibrogenic mechanisms are operating at the early onset of renal fibrosis and its contribution declines with the progression in mouse unilateral ureteral obstruction (UUO) model. The aim of the study is to evaluate the renal fibrogenic potential of FG4592, a recently approved orally active HIF prolyl hydroxylase inhibitor in mouse UUO model. Male C57BL/6J mice orally given FG-4592 (12.5 mg/kg/day and 50 mg/kg/day) were subjected to UUO. Neither dose of FG-4592 affected renal fibrosis or macrophage infiltration. FG-4592 had no effects on increased mRNA of collagen I, collagen III or transforming growth factor-β1. At 3 days after UUO, higher dose of FG-4592 potentiated the increased mRNA expression of profibrogenic molecules, plasminogen activator inhibitor 1 (Pai-1) and connective tissue growth factor (Ctgf) but such potentiation disappeared at 7 days after UUO. It is suggested that FG-4592 used in the present study had little effects on renal fibrosis even though high dose of FG-4592 used in the present study transiently potentiated gene expression of Pai-1 and Ctgf in the UUO kidney.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:142 |
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| Enthalten in: |
Journal of pharmacological sciences - 142(2020), 3 vom: 10. März, Seite 93-100 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kabei, Kazuya [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 03.09.2020 Date Revised 11.01.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.jphs.2019.12.002 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM304665118 |
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| 245 | 1 | 0 | |a Effects of orally active hypoxia inducible factor alpha prolyl hydroxylase inhibitor, FG4592 on renal fibrogenic potential in mouse unilateral ureteral obstruction model |
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| 520 | |a Copyright © 2019 The Authors. Production and hosting by Elsevier B.V. All rights reserved. | ||
| 520 | |a Orally active hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitors that stabilize HIF protein and stimulate the production of erythropoietin have been approved to treat renal anemia. Our previous report suggested that HIF-1α dependent fibrogenic mechanisms are operating at the early onset of renal fibrosis and its contribution declines with the progression in mouse unilateral ureteral obstruction (UUO) model. The aim of the study is to evaluate the renal fibrogenic potential of FG4592, a recently approved orally active HIF prolyl hydroxylase inhibitor in mouse UUO model. Male C57BL/6J mice orally given FG-4592 (12.5 mg/kg/day and 50 mg/kg/day) were subjected to UUO. Neither dose of FG-4592 affected renal fibrosis or macrophage infiltration. FG-4592 had no effects on increased mRNA of collagen I, collagen III or transforming growth factor-β1. At 3 days after UUO, higher dose of FG-4592 potentiated the increased mRNA expression of profibrogenic molecules, plasminogen activator inhibitor 1 (Pai-1) and connective tissue growth factor (Ctgf) but such potentiation disappeared at 7 days after UUO. It is suggested that FG-4592 used in the present study had little effects on renal fibrosis even though high dose of FG-4592 used in the present study transiently potentiated gene expression of Pai-1 and Ctgf in the UUO kidney | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a FG-4592 | |
| 650 | 4 | |a Hypoxia-inducible factor | |
| 650 | 4 | |a Prolyl hydroxylase domain-containing protein | |
| 650 | 4 | |a Renal fibrosis | |
| 650 | 7 | |a Hif1a protein, mouse |2 NLM | |
| 650 | 7 | |a Hypoxia-Inducible Factor 1, alpha Subunit |2 NLM | |
| 650 | 7 | |a Isoquinolines |2 NLM | |
| 650 | 7 | |a Prolyl-Hydroxylase Inhibitors |2 NLM | |
| 650 | 7 | |a Glycine |2 NLM | |
| 650 | 7 | |a TE7660XO1C |2 NLM | |
| 650 | 7 | |a roxadustat |2 NLM | |
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| 700 | 1 | |a Tateishi, Yu |e verfasserin |4 aut | |
| 700 | 1 | |a Shiota, Masayuki |e verfasserin |4 aut | |
| 700 | 1 | |a Osada-Oka, Mayuko |e verfasserin |4 aut | |
| 700 | 1 | |a Nishide, Shunji |e verfasserin |4 aut | |
| 700 | 1 | |a Uchida, Junji |e verfasserin |4 aut | |
| 700 | 1 | |a Nakatani, Tatsuya |e verfasserin |4 aut | |
| 700 | 1 | |a Matsunaga, Shinji |e verfasserin |4 aut | |
| 700 | 1 | |a Yamaguchi, Takehiro |e verfasserin |4 aut | |
| 700 | 1 | |a Tomita, Shuhei |e verfasserin |4 aut | |
| 700 | 1 | |a Miura, Katsuyuki |e verfasserin |4 aut | |
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