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HIF1alpha synergizes with glucocorticoids to promote BFU-E progenitor self-renewal.
Flygare, Johan; Rayon Estrada, Violeta; Shin, Chanseok; Gupta, Sumeet; Lodish, Harvey F.
Afiliação
  • Flygare J; Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Blood ; 117(12): 3435-44, 2011 Mar 24.
Article em En | MEDLINE | ID: mdl-21177435
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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Células Precursoras Eritroides / Proliferação de Células / Subunidade alfa do Fator 1 Induzível por Hipóxia / Glucocorticoides Limite: Animals Idioma: En Revista: Blood Ano de publicação: 2011 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Células Precursoras Eritroides / Proliferação de Células / Subunidade alfa do Fator 1 Induzível por Hipóxia / Glucocorticoides Limite: Animals Idioma: En Revista: Blood Ano de publicação: 2011 Tipo de documento: Article País de afiliação: Estados Unidos