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Article Dans Une Revue Cellular Signalling Année : 2022

Indoxyl sulfate impairs erythropoiesis at BFU-E stage in chronic kidney disease

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Laure Santier
  • Fonction : Auteur
Ziad Massy
  • Fonction : Auteur

Résumé

Chronic kidney disease (CKD) is a global health condition characterized by a progressive deterioration of kidney function. It is associated with high serum levels of uremic toxins (UT), such as Indoxyl Sulfate (IS), which may participate in the genesis of several uremic complications. Anemia is one of the major complications in CKD patients that contribute to cardiovascular disease, increase morbi-mortality, and is associated with a deterioration of kidney failure in these patients. Our study aimed to characterize the impact of IS on CKD-related erythropoiesis. Using cellular and pre-clinical models, we studied cellular and molecular effects of IS on the growth and differentiation of erythroid cells. First, we examined the effect of clinically relevant concentrations of IS (up to 250 μM) in the UT7/EPO cell line. IS at 250 μM increased apoptosis of UT7/EPO cells at 48 h compared to the control condition. We confirmed this apoptotic effect of IS in erythropoiesis in human primary CD34+ cells during the later stages of erythropoiesis. Then, in IS-treated human primary CD34+ cells and in a (5/6 Nx) mice model, a blockage at the burst-forming unit-erythroid (BFU-E) stage of erythropoiesis was also observed. Finally, IS deregulates a number of erythropoietic related genes such as GATA-1, Erythropoietin-Receptor (EPO-R), and β-globin. Our findings suggest that IS could affect cell viability and differentiation of erythroid progenitors by altering erythropoiesis and contributing to the development of anemia in CKD.
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Dates et versions

hal-03924871 , version 1 (05-01-2023)

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Citer

Eya Hamza, Mercedes Vallejo-Mudarra, Hakim Ouled-Haddou, Cristina García-Caballero, Melania Guerrero-Hue, et al.. Indoxyl sulfate impairs erythropoiesis at BFU-E stage in chronic kidney disease. Cellular Signalling, 2022, pp.110583. ⟨10.1016/j.cellsig.2022.110583⟩. ⟨hal-03924871⟩
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