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1000
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Abstract/Summary
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Erythropoietin (EPO) is the key hormone responsible for red blood cell production. It is produced in specialized renal EPO-producing (REP) cells, which, however, lose their ability to produce EPO in chronic kidney disease - one of the main causes of renal anemia. Our project aimed to investigate the plasticity, signaling pathways, and differentiation potential of REP cells with and without treatment using the PHD inhibitor Roxdustat (Roxa) to develop new therapeutic strategies. Using pharmacological approaches (Roxa treatment), the project has yielded several important findings. Roxa not only increased systemic erythropoiesis but also expanded a renal Sca-1⁺ mesenchymal stem-like cell population with temporary EPO-producing capacity and immunomodulatory properties, highlighting the heterogeneity of the renal interstitium. Additionally, conditionally immortalized REP-derived cells (REPD) demonstrated remarkable plasticity, with pericytic and neuroglial features, and exhibited a switch-like induction of EPO under hypoxia, confirming the unique regulation of EPO expression. REPD cells also formed tunneling nanotubes, suggesting structural and functional integration into the vascular niche. These findings emphasize REP cells as highly plastic, multipotent cells crucial for oxygen sensing and vascular support. They enhance our understanding of the pathophysiology of renal anemia.
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