Brisot Emma, Leprêtre Pierre-Marie, Hamza Eya, Fourdinier Ophélie, Brigant Benjamin, Ouled-Haddou Hakim, Choukroun Gabriel, Massy Ziad A, Verbeke Francis, Metzinger-Le Meuth Valérie, Glorieux Griet, Metzinger Laurent
UPJV, HEMATIM UR 4666, C.U.R.S, Université de Picardie Jules Verne, CEDEX 1, 80025, Amiens, France.
CETAPS UR 3882, Boulevard André Siegfried, University of Rouen Normandie, 76000, Rouen, France.
Noncoding RNA Res. 2025 May 2;13:121-130. doi: 10.1016/j.ncrna.2025.04.009. eCollection 2025 Aug.
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 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.
慢性肾脏病（CKD）构成了重大威胁，心血管疾病和全因死亡率有所上升。贫血在CKD中很常见，与血液中尿毒症毒素的蓄积有关。我们之前在细胞和临床前CKD模型中证明，尿毒症毒素硫酸吲哚酚（IS）会影响红细胞生成的调节。在此，我们评估了非编码RNA在这种毒性作用中的作用。使用纳米串技术在人红细胞生成细胞系UT7/EPO中测量了IS对微小RNA表达的影响。我们发现用IS处理的细胞中miR-223显著增加。这一发现在人原代CD34细胞中得到了进一步验证，CD34细胞是更接近人体红细胞生成的生理模型。最后，在不同阶段的CKD患者中，miR-223的血清水平与包括IS在内的代表性尿毒症毒素相关，也与内皮功能障碍标志物相关，表明与血管损伤有关。这些相关性因促红细胞生成素治疗和透析情况而异。这些发现表明，miR-223可能在CKD贫血的发生发展中起作用。需要进一步研究miR-223在红细胞生成中的作用，以更好地理解CKD贫血的潜在机制以及尿毒症毒素的潜在作用。最终，这可能为CKD贫血的治疗开辟新的途径。
