03252nam a2200409 c 4500 99376082276206441 DE-605 20250905125700.0 cr#||||||||||| 250903s2025 gw |||| o ||| | eng c 10.4126/FRL01-006499176 doi (DE-605)HT031267419 (DE-599)HBZHT031267419 DE-38M ger DE-38M DE-38M rda eng XA-DE DE-98 DE-38M 610 Katschinski, Dörthe (DE-588)1375532529 aut Verfasser Prolyl-4-hydroxylase domain (PHD) enzymes and erythropoietin producing mesenchymal stem cell (MSC) like cells in the kidney final report name of the applicant: Prof. Dr. med. Dörthe M. Katschinski ; Deutsche Forschungsgemeinschaft Göttingen Institut für Herz- und Kreislaufphysiologie - Universitätsmedizin Göttingen [2025] 1 Online-Ressource (9 Seiten) Text txt rdacontent Computer c rdamedia Online-Ressource cr rdacarrier DFG final report ; reporting period (entire funding period): January 2020 – November ; DFG reference number: Ka1269/13-1 ; project number: AOBJ, 659357 Open Access Unrestricted online access star 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. Bericht (DE-588)4128022-2 gnd-content Universitätsmedizin Göttingen Institut für Herz- und Kreislaufphysiologie (DE-588)1375522744 oth Sonstige Deutsche Forschungsgemeinschaft (DE-588)2007744-0 spn Sponsor https://repository.publisso.de/resource/frl:6499176 Volltext kostenfrei 99376082276206441 DE-98 NRW d 99376082276206441 DE-38M NRW d iall OA 38 M: ellinet; GND: (DE-588)1375522744