The HIFα-Stabilizing Drug Roxadustat Increases the Number of Renal Epo-Producing Sca-1+ Cells

Cells

卷:11

Kai Oliver Böker¹  Jia Guo²  Katja Brechtel-Curth²  Aline Jatho²  Dörthe M. Katschinski²  Anke Zieseniss²  Gabriela Salinas³  Roland H. Wenger⁴ 

[1] Department of Trauma Surgery, Orthopaedics and Plastic Surgery, University Medical Center Göttingen, Georg-August-University Göttingen, 37075 Goettingen, Germany;

[2] Institute of Cardiovascular Physiology, University Medical Center Göttingen, Georg-August-University Göttingen, 37073 Goettingen, Germany;

[3] NGS-Integrative Genomics Core Unit (NIG), Institute of Human Genetics, University Medical Center Göttingen, Georg-August-University Göttingen, 37073 Goettingen, Germany;

[4] National Centre of Competence in Research “Kidney.CH”, 8057 Zurich, Switzerland;

关键词: HIFα-stabilizing drugs;    PHD inhibitor;    roxadustat;    erythropoietin;    Sca-1;   

DOI  :  10.3390/cells11040753

来源: DOAJ

【 摘 要 】

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⁺ mesenchymal cells following roxadustat treatment increased exclusively in the kidneys. Isolated Sca-1⁺ 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⁺ 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⁺ 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.

【 授权许可】

Unknown