Publications by authors named "Taku Nakai"

During mammalian development, production sites of the erythroid growth factor erythropoietin (EPO) shift from the neural tissues to the liver in embryos and to the kidneys in adults. Embryonic neural EPO-producing (NEP) cells, a subpopulation of neuroepithelial and neural crest cells, express the gene between embryonic day (E) 8.5 and E11.

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  • Erythropoiesis, or the production of red blood cells, is stimulated by low-oxygen conditions (hypoxia) to ensure adequate oxygen supply, primarily involving hemoglobin which contains iron.
  • Iron metabolism is closely regulated to prevent oxidative stress, and hypoxia triggers the mobilization of stored iron for hemoglobin production via the erythroid growth factor, erythropoietin (EPO), secreted by renal EPO-producing cells in the kidneys.
  • Recent studies highlight the connections between hypoxia-induced EPO production, red blood cell formation, and iron regulation, while also exploring disease mechanisms related to these processes and suggesting future research into using renal cells from kidney patients for better understanding and treatment of chronic kidney disease
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  • Kidney disease leads to anemia mainly due to reduced production of erythropoietin (EPO), which is regulated by hypoxia-inducible transcription factors (HIFs); HIF-PH inhibitors help reactivate EPO production in renal anemia patients.
  • This study found that different HIF-PH inhibitors, when administered to mice, can specifically alter EPO gene expression in the kidney and liver, each with unique drug characteristics affecting pharmacokinetics and iron metabolism.
  • The findings highlight that targeting renal EPO induction is crucial for the effectiveness of HIF-PH inhibitors, offering insights for choosing the right treatment for individual renal anemia patients.
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The erythroid growth factor erythropoietin (EPO) is mainly produced by the kidneys in adult mammals and induces expansion of erythroid cells and iron use for hemoglobin synthesis. The liver also produces EPO at a lower level than the kidneys. Renal and hepatic EPO production is fundamentally regulated by hypoxia-inducible transcription factors (HIFs) in a hypoxia/anemia-inducible manner.

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Kidney injury often causes anemia due to a lack of production of the erythroid growth factor erythropoietin (EPO) in the kidneys. Roxadustat is one of the first oral medicines inducing EPO production in patients with renal anemia by activating hypoxia-inducible factors (HIFs), which are activators of EPO gene expression. In this study, to develop prodrugs of roxadustat with improved permeability through cell membrane, we investigated the effects of 8 types of esterification on the pharmacokinetics and bioactivity of roxadustat using Hep3B hepatoma cells that HIF-dependently produce EPO.

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  • Space travel negatively affects health due to environmental stresses like microgravity and radiation, impacting kidney function, blood pressure, and bone health.
  • A study examined the role of the Nrf2 protein in kidney function in mice after a 31-day mission on the International Space Station, revealing changes in gene expressions related to these bodily functions.
  • Results showed that certain genes, particularly Ugt1a isoforms, were induced in the kidneys post-spaceflight to help excrete excess lipids, highlighting the kidneys' important role in adapting to gravity changes during space travel.
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Renal interstitial fibroblasts are responsible for producing the erythroid growth factor Epo and the vasopressor renin in addition to kidney fibrosis, in which they are transformed into myofibroblasts. Therefore, analyses of fibroblasts may elucidate the complex mechanisms of kidney diseases. However, the fragility of these cells makes their isolation for analyses and cultivation difficult.

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Background: Erythrocyte mass contributes to maintaining systemic oxygen delivery and blood viscosity, with the latter being one of the determinants of blood pressure. However, the physiological response to blood pressure changes under anaemic conditions remain unknown.

Methods And Findings: We show that anaemia decreases blood pressure in human patients and mouse models.

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The erythroid growth factor erythropoietin (Epo) is produced by renal interstitial fibroblasts, called REP (renal Epo-producing) cells, in a hypoxia-inducible manner. In chronic kidney disease (CKD), REP cells lose their Epo-production ability, leading to renal anaemia. Concurrently, REP cells are suggested to be transformed into myofibroblasts, which are the major player of renal fibrosis.

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