Mechanisms of differential transferrin receptor expression in normal hematopoiesis

摘要: We have investigated the expression of transferrin receptor (TfR) iron regulatory protein-1 (IRP-1) and protein-2 (IRP-2) in liquid suspension culture purified hematopoietic progenitor cells (HPCs) induced by a growth factor stimulus to proliferation unilineage differentiation/maturation through erythroid, granulocytic, monocytic megakaryocytic lineages. In initial HPC differentiation, TfR is both erythroid granulopoietic cultures. late differentiation (i.e. starting from day 5 culture) then differentiated precursor maturation, gene highly expressed lineage, whereas it sharply downmodulated granulopoietic, monocytopoietic series. The elevated is: (a) mediated high rate transcription; (b) modulated intracellular levels; (c) mRNA stabilization protein (IRP), that IRP-1 activity lineage as compared levels observed other hemopoietic lineages; (d) dependent on exogenous erythropoietin (Epo) (this indicated marked IRP-1/IRP-2 downmodulation after Epo starvation). Interestingly, analysis IRP-2 during showed that: was maintained all steps while lost stages four However, are when monocytes, which express only low IRP-2, maturation macrophages. These studies indicate normal erythropoiesis, hyperexpression TfR, early Epo-dependent via transcriptional post-transcriptional mechanisms; pathways, first (the latter phenomenon suppression IRP inactivation).