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Details

Autor(en) / Beteiligte
Titel
HIF1α synergizes with glucocorticoids to promote BFU-E progenitor self-renewal
Ist Teil von
  • Blood, 2011-03, Vol.117 (12), p.3435-3444
Ort / Verlag
Washington, DC: Elsevier Inc
Erscheinungsjahr
2011
Link zum Volltext
Quelle
Alma/SFX Local Collection
Beschreibungen/Notizen
  • With the aim of finding small molecules that stimulate erythropoiesis earlier than erythropoietin and that enhance erythroid colony-forming unit (CFU-E) production, we studied the mechanism by which glucocorticoids increase CFU-E formation. Using erythroid burst-forming unit (BFU-E) and CFU-E progenitors purified by a new technique, we demonstrate that glucocorticoids stimulate the earliest (BFU-E) progenitors to undergo limited self-renewal, which increases formation of CFU-E cells > 20-fold. Interestingly, glucocorticoids induce expression of genes in BFU-E cells that contain promoter regions highly enriched for hypoxia-induced factor 1α (HIF1α) binding sites. This suggests activation of HIF1α may enhance or replace the effect of glucocorticoids on BFU-E self-renewal. Indeed, HIF1α activation by a prolyl hydroxylase inhibitor (PHI) synergizes with glucocorticoids and enhances production of CFU-Es 170-fold. Because PHIs are able to increase erythroblast production at very low concentrations of glucocorticoids, PHI-induced stimulation of BFU-E progenitors thus represents a conceptually new therapeutic window for treating erythropoietin-resistant anemia.
Sprache
Englisch
Identifikatoren
ISSN: 0006-4971
eISSN: 1528-0020
DOI: 10.1182/blood-2010-07-295550
Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3069680

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