#3777 ACTIVATION OF HYPOXIA-INDUCIBLE FACTORS IN ERYTHROID PROGENITOR CELLS RESULTS IN DEFECTIVE ERYTHROPOIESIS

Abstract Background and Aims Hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) activates HIF in renal pericytes fibroblasts to promote erythropoietin production erythropoiesis. However, the effects of stabilization erythroid lineage are not clear. We aim study lineage-specific on erythropoiesis by preclinical models. Method EporGFP-Cre/+;VhlF/F mice were used achieve HIF. Surface expression TER-119, CD44, forward scatter (FSC) define erythroblast, reticulocyte, red blood cell bone marrow. Expression propidium iodide surface annexin V apoptosis. Stress was induced subcutaneous administration phenylhydrazine. Results Compared with littermate VhlF/F mice, had decreased hematocrit, percentage erythroblasts marrow, increased apoptosis marrow under steady state. These phenotypes defective normalized harboring concomitant Vhl, Hif1a, Hif2a deletion (EporGFP-Cre/+;VhlF/F;Hif1aF/F;Hif2aF/Fmice). Although macrophages also express Epor, macrophage-specific Vhl either Tg(Csf1r-CreESR1);VhlF/F or Lyz2Cre/+;VhlF/F did result During stress erythropoiesis, compared similar lower erythroblast spleen. Conclusion progenitor cells impairs murine The partially reversed during