The HIFα-Stabilizing Drug Roxadustat Increases the Number of Renal Epo-Producing Sca-1<sup>+</sup> Cells
Inhibition of the prolyl-4-hydroxylase domain (PHD) enzymes, leading to the stabilization of hypoxia-inducible factor (HIF) α as well as to the stimulation of erythropoietin (Epo) synthesis, is the functional mechanism of the new anti-anemia drug roxadustat. Little is known about the effects of roxa...
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MDPI AG
2022-02-01
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| Online Access: | https://www.mdpi.com/2073-4409/11/4/753 |
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| author | Aline Jatho Anke Zieseniss Katja Brechtel-Curth Jia Guo Kai Oliver Böker Gabriela Salinas Roland H. Wenger Dörthe M. Katschinski |
| author_facet | Aline Jatho Anke Zieseniss Katja Brechtel-Curth Jia Guo Kai Oliver Böker Gabriela Salinas Roland H. Wenger Dörthe M. Katschinski |
| author_sort | Aline Jatho |
| collection | DOAJ |
| description | Inhibition of the prolyl-4-hydroxylase domain (PHD) enzymes, leading to the stabilization of hypoxia-inducible factor (HIF) α as well as to the stimulation of erythropoietin (Epo) synthesis, is the functional mechanism of the new anti-anemia drug roxadustat. Little is known about the effects of roxadustat on the Epo-producing cell pool. To gain further insights into the function of PHD inhibitors, we characterized the abundance of mesenchymal stem cell (MSC)-like cells after roxadustat treatment of mice. The number of Sca-1<sup>+</sup> mesenchymal cells following roxadustat treatment increased exclusively in the kidneys. Isolated Sca-1<sup>+</sup> cells demonstrated typical features of MSC-like cells, including adherence to tissue culture plates, trilineage differentiation potential, and expression of MSC markers. Kidney-derived Sca-1<sup>+</sup> MSC-like cells were cultured for up to 21 days. Within the first few days in culture, cells stabilized HIF-1α and HIF-2α and temporarily increased Epo production upon incubation in hypoxia. In summary, we have identified a Sca-1<sup>+</sup> MSC-like cell population that is involved in renal Epo production and might contribute to the strong anti-anemic effect of the PHD inhibitor roxadustat. |
| first_indexed | 2024-03-09T22:20:01Z |
| format | Article |
| id | doaj.art-424aef703446484f8917f85d6a28e77b |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T22:20:01Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-424aef703446484f8917f85d6a28e77b2023-11-23T19:16:27ZengMDPI AGCells2073-44092022-02-0111475310.3390/cells11040753The HIFα-Stabilizing Drug Roxadustat Increases the Number of Renal Epo-Producing Sca-1<sup>+</sup> CellsAline Jatho0Anke Zieseniss1Katja Brechtel-Curth2Jia Guo3Kai Oliver Böker4Gabriela Salinas5Roland H. Wenger6Dörthe M. Katschinski7Institute of Cardiovascular Physiology, University Medical Center Göttingen, Georg-August-University Göttingen, 37073 Goettingen, GermanyInstitute of Cardiovascular Physiology, University Medical Center Göttingen, Georg-August-University Göttingen, 37073 Goettingen, GermanyInstitute of Cardiovascular Physiology, University Medical Center Göttingen, Georg-August-University Göttingen, 37073 Goettingen, GermanyInstitute of Cardiovascular Physiology, University Medical Center Göttingen, Georg-August-University Göttingen, 37073 Goettingen, GermanyDepartment of Trauma Surgery, Orthopaedics and Plastic Surgery, University Medical Center Göttingen, Georg-August-University Göttingen, 37075 Goettingen, GermanyNGS-Integrative Genomics Core Unit (NIG), Institute of Human Genetics, University Medical Center Göttingen, Georg-August-University Göttingen, 37073 Goettingen, GermanyNational Centre of Competence in Research “Kidney.CH”, 8057 Zurich, SwitzerlandInstitute of Cardiovascular Physiology, University Medical Center Göttingen, Georg-August-University Göttingen, 37073 Goettingen, GermanyInhibition of the prolyl-4-hydroxylase domain (PHD) enzymes, leading to the stabilization of hypoxia-inducible factor (HIF) α as well as to the stimulation of erythropoietin (Epo) synthesis, is the functional mechanism of the new anti-anemia drug roxadustat. Little is known about the effects of roxadustat on the Epo-producing cell pool. To gain further insights into the function of PHD inhibitors, we characterized the abundance of mesenchymal stem cell (MSC)-like cells after roxadustat treatment of mice. The number of Sca-1<sup>+</sup> mesenchymal cells following roxadustat treatment increased exclusively in the kidneys. Isolated Sca-1<sup>+</sup> cells demonstrated typical features of MSC-like cells, including adherence to tissue culture plates, trilineage differentiation potential, and expression of MSC markers. Kidney-derived Sca-1<sup>+</sup> MSC-like cells were cultured for up to 21 days. Within the first few days in culture, cells stabilized HIF-1α and HIF-2α and temporarily increased Epo production upon incubation in hypoxia. In summary, we have identified a Sca-1<sup>+</sup> MSC-like cell population that is involved in renal Epo production and might contribute to the strong anti-anemic effect of the PHD inhibitor roxadustat.https://www.mdpi.com/2073-4409/11/4/753HIFα-stabilizing drugsPHD inhibitorroxadustaterythropoietinSca-1 |
| spellingShingle | Aline Jatho Anke Zieseniss Katja Brechtel-Curth Jia Guo Kai Oliver Böker Gabriela Salinas Roland H. Wenger Dörthe M. Katschinski The HIFα-Stabilizing Drug Roxadustat Increases the Number of Renal Epo-Producing Sca-1<sup>+</sup> Cells Cells HIFα-stabilizing drugs PHD inhibitor roxadustat erythropoietin Sca-1 |
| title | The HIFα-Stabilizing Drug Roxadustat Increases the Number of Renal Epo-Producing Sca-1<sup>+</sup> Cells |
| title_full | The HIFα-Stabilizing Drug Roxadustat Increases the Number of Renal Epo-Producing Sca-1<sup>+</sup> Cells |
| title_fullStr | The HIFα-Stabilizing Drug Roxadustat Increases the Number of Renal Epo-Producing Sca-1<sup>+</sup> Cells |
| title_full_unstemmed | The HIFα-Stabilizing Drug Roxadustat Increases the Number of Renal Epo-Producing Sca-1<sup>+</sup> Cells |
| title_short | The HIFα-Stabilizing Drug Roxadustat Increases the Number of Renal Epo-Producing Sca-1<sup>+</sup> Cells |
| title_sort | hifα stabilizing drug roxadustat increases the number of renal epo producing sca 1 sup sup cells |
| topic | HIFα-stabilizing drugs PHD inhibitor roxadustat erythropoietin Sca-1 |
| url | https://www.mdpi.com/2073-4409/11/4/753 |
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