Publications by authors named "Rafiou Agoro"

A number of studies have reported an association between phosphorus, red blood cell (RBC) production, and iron metabolism. However, it is difficult to distinguish whether the effect of phosphorus is direct or through the actions of FGF23, and it is not clear whether phosphorus is positively or negatively associated with RBC production. In the present study, we investigated the effects of a) increased phosphorus load and b) phosphorus deficiency on erythropoiesis and iron metabolism in association with FGF23.

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A milestone in sickle cell disease (SCD) therapeutics was achieved in December 2023 with the FDA-approved gene therapy for patients aged 12 years and older. However, these therapies may only suit a fraction of patients because of cost or health risks. A better understanding of SCD outcome heterogeneity is needed to propose patient-specific pharmacological interventions.

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Unlabelled: FGF23 via its coreceptor αKlotho (KL) provides critical control of phosphate metabolism, which is altered in rare and very common syndromes, however the spatial-temporal mechanisms dictating renal FGF23 functions remain poorly understood. Thus, developing approaches to modify specific FGF23-dictated pathways has proven problematic. Herein, wild type mice were injected with rFGF23 for 1, 4 and 12h and renal FGF23 bioactivity was determined at single cell resolution.

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Introduction: Due to a lack of spatial-temporal resolution at the single cell level, the etiologies of the bone dysfunction caused by diseases such as normal aging, osteoporosis, and the metabolic bone disease associated with chronic kidney disease (CKD) remain largely unknown.

Methods: To this end, flow cytometry and scRNAseq were performed on long bone cells from Sost-cre/Ai9 mice, and pure osteolineage transcriptomes were identified, including novel osteocyte-specific gene sets.

Results: Clustering analysis isolated osteoblast precursors that expressed , , and , and a mature osteoblast population defined by , , and .

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Osteocytes act within a hypoxic environment to control key steps in bone formation. FGF23, a critical phosphate-regulating hormone, is stimulated by low oxygen/iron in acute and chronic diseases, however the molecular mechanisms directing this process remain unclear. Our goal was to identify the osteocyte factors responsible for FGF23 production driven by changes in oxygen/iron utilization.

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The bone-derived hormone fibroblast growth factor 23 (FGF23) functions in concert with parathyroid hormone (PTH) and the active vitamin D metabolite, 1,25(OH) vitamin D (1,25D), to control phosphate and calcium homeostasis. A rise in circulating levels of phosphate and 1,25D leads to FGF23 production in bone. Circulating FGF23 acts on the kidney by binding to FGF receptors and the co-receptor α-Klotho to promote phosphaturia and reduce circulating 1,25D levels.

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Purpose Of Review: Chronic kidney disease (CKD) is a progressive disorder that is associated with development of elevated fibroblast growth factor 23 (FGF23) levels and anemia. Here, we review recent literature that extends our current knowledge on the interactions between FGF23 and anemia in CKD and the impact of anemia-targeting therapeutics on FGF23 elevation in CKD.

Recent Findings: The anemia of CKD is primarily driven by a lack of erythropoietin (EPO) and iron deficiency.

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Ferric citrate (FC) is an approved therapy for chronic kidney disease (CKD) patients as a phosphate (Pi) binder for dialysis-dependent CKD, and for iron deficiency anemia (IDA) in non-dialysis CKD. Elevated Pi and IDA both lead to increased FGF23, however, the roles of iron and FGF23 during CKD remain unclear. To this end, iron and Pi metabolism were tested in a mouse model of CKD (0.

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Article Synopsis
  • Fibroblast growth factor-23 (FGF23) is linked to increased mortality and mineral imbalances in chronic kidney disease (CKD), with anemia being a significant factor driving its increase.
  • A study using mice with CKD tested the effects of the HIF-PHI drug BAY 85-3934 (Molidustat), which successfully raised erythropoietin (EPO) levels and improved anemia while significantly reducing FGF23 levels and blood urea nitrogen (BUN).
  • The treatment also did not worsen bone health parameters, suggesting that addressing anemia in CKD can improve related dysfunctions without adverse effects on bone integrity.
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FGF23 interacts with a FGFR/KL-receptor complex to propagate cellular signaling, where its C-terminal C26 peptide is critical for engaging the co-receptor KL. We identify a distinct peptide sequence C28 residing in the FGF23 C terminus that regulates its interaction with KL. C28 can independently function as an FGF23 antagonist, and we report an optimized peptide antagonist of much enhanced potency.

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Osteocytes, which represent up to 95% of adult skeletal cells, are deeply embedded in bone. These cells exhibit important interactive abilities with other bone cells such as osteoblasts and osteoclasts to control skeletal formation and resorption. Beyond this local role, osteocytes can also influence the function of distant organs due to the presence of their sophisticated lacunocanalicular system, which connects osteocyte dendrites directly to the vasculature.

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Iron-deficiency anemia is a potent stimulator of the phosphaturic hormone Fibroblast growth factor-23 (FGF23). Anemia, elevated FGF23, and elevated serum phosphate are significant mortality risk factors for patients with chronic kidney disease (CKD). However, the contribution of anemia to overall circulating FGF23 levels in CKD is not understood.

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Hypoferremia results as an acute phase response to infection and inflammation aiming to reduce iron availability to pathogens. Activation of toll-like receptors (TLRs), the key sensors of the innate immune system, induces hypoferremia mainly through the rise of the iron hormone hepcidin. Conversely, stimulation of erythropoiesis suppresses hepcidin expression via induction of the erythropoietin-responsive hormone erythroferrone.

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Iron is an essential element that is required for oxygen transfer, redox, and metabolic activities in mammals and bacteria. Mycobacteria, some of the most prevalent infectious agents in the world, require iron as growth factor. Mycobacterial-infected hosts set up a series of defense mechanisms, including systemic iron restriction and cellular iron distribution, whereas mycobacteria have developed sophisticated strategies to acquire iron from their hosts and to protect themselves from iron's harmful effects.

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Macrophages play crucial roles in innate immune response and in the priming of adaptive immunity, and are characterized by their phenotypic heterogeneity and plasticity. Reprogramming intracellular metabolism in response to microenvironmental signals is required for M1/M2 macrophage polarization and function. Here we assessed the influence of iron on the polarization of the immune response in vivo and in vitro.

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Severe anemia and iron deficiency are common complications in chronic kidney disease. The cause of renal anemia is multifactorial and includes decreased erythropoietin (Epo) production, iron deficiency, and inflammation, and it is currently treated with injections of synthetic Epo. However, the use of recombinant Epo has several adverse effects.

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Background: Recent evidence indicates a robust competition between the host and mycobacteria for iron acquisition during mycobacterial infection. Variable effects of iron supplementation on the susceptibility to mycobacterial infection have been reported. In this study, we revisited the effects of an experimental iron-enriched diet on Mycobacterium bovis bacille Calmette-Guerin (BCG) infection.

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Article Synopsis
  • - Allergic asthma involves a strong Th2 immune response, which is triggered by the protease allergen papain that induces rapid inflammation in the lungs, characterized by an influx of inflammatory cells, especially eosinophils and neutrophils.
  • - In this study, mice were exposed to papain via intranasal administration, leading to a quick release of inflammatory cytokines like IL-1α, IL-1β, and IL-33, with the inflammatory response drastically reduced in mice lacking IL-1R1 and MyD88.
  • - Research indicated that multiple cell types contribute to the inflammatory response to papain, as deleting MyD88 in specific cells only partially inhibited the reaction, while the IL-
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Iron is essential in all organisms. In mammals systemic iron homeostasis relies on hepcidin, a peptide hormone with defensin properties, and its target, the cell iron exporter ferroportin. Hepcidin and ferroportin transcription are both upregulated by high iron levels, but are inversely regulated upon inflammation, leading to hypoferremia.

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