Uremic toxins levels are associated with miR-223 in chronic kidney disease-associated anemia
Chronic kidney disease (CKD) poses a significant threat, with increased rates of cardiovascular and all-cause mortality. Anemia, common in CKD, is associated with accumulation of uremic toxins in the bloodstream. We previously demonstrated that the uremic toxin indoxyl sulfate (IS) impacts the regulation of erythropoiesis in cellular and preclinical CKD models. Here, the role of non-coding RNAs in this toxic effect was evaluated. The effect of IS on microRNA expression was measured in human erythropoietic cell line UT7/EPO, using nanostring. We found a significant increase of miR-223 in cells treated with IS. This finding was further validated in human primary CD34<sup>+</sup> cells, a more physiological model for human erythropoiesis. Finally, serum levels of miR-223 correlated with representative uremic toxins, including IS, in patients with various stages of CKD, and also with endothelial dysfunction markers, indicating a link with vascular damage. These correlations varied according to erythropoietin treatment and dialysis. These findings suggest that miR-223 may play a role in the development of anemia in CKD. Further investigation into the involvement of miR-223 in erythropoiesis is needed for a better understanding of the mechanisms underlying anemia in CKD and the potential role of uremic toxins. Ultimately, this may open up new therapeutic possibilities for the management of anemia in CKD.
Authors
- Hakim Ouled‐Haddou (ORCID: https://orcid.org/0000-0002-3342-1288)
- Ophélie Fourdinier
- Eya Hamza (ORCID: https://orcid.org/0000-0002-8881-381X)
- Valérie Metzinger‐Le Meuth (ORCID: https://orcid.org/0000-0003-1718-5083)
- Francis Verbeke (ORCID: https://orcid.org/0000-0003-2112-6326)
- Gabriel Choukroun (ORCID: https://orcid.org/0000-0003-0772-5656)
- Benjamin Brigant (ORCID: https://orcid.org/0000-0003-4977-6750)
- Pierre‐Marie Leprêtre (ORCID: https://orcid.org/0000-0002-5149-2768)
- Laurent Metzinger (ORCID: https://orcid.org/0000-0002-7636-8480)
- Ziad A. Massy (ORCID: https://orcid.org/0000-0001-5771-5996)
- Griet Glorieux (ORCID: https://orcid.org/0000-0002-7641-4707)
- Emma Brisot
Institutions
- Université Paris-Sud (FR)
- Inserm (FR)
- Université de Versailles Saint-Quentin-en-Yvelines (FR)
- Norwegian University of Science and Technology (NO)
- Ghent University Hospital (BE)
- Sorbonne Université (FR)
- Université Sorbonne Paris Nord (FR)
- Centre Hospitalier Universitaire Amiens-Picardie (FR)
- Assistance Publique – Hôpitaux de Paris (FR)
- Centre de recherche en Epidémiologie et Santé des Populations (FR)
- Hôpital Ambroise-Paré (FR)
- Laboratoire de Recherche Vasculaire Translationnelle (FR)
- Association pour l'Utilisation du Rein Artificiel (FR)
- Université de Picardie Jules Verne (FR)
- Université de Rouen Normandie (FR)
Publication Details
- Journal
- Non-coding RNA Research
- Published
- 2025-05-02
- DOI
- https://doi.org/10.1016/j.ncrna.2025.04.009
- Citations
- 3
- Primary Topic
- MicroRNA in disease regulation
- Type
- article
- Field-Weighted Citation Impact
- 2.81
Funders
- Ministère de l'Enseignement supérieur, de la Recherche et de l'Innovation
- Vifor Pharma