Thrombospondin 1, produced by endothelial cells under the action of erythropoietin, stimulates thymidine incorporation into erythroid cells and counteracts the inhibitory action of insulin-like growth factor binding protein 3.
The nature of erythropoietin (EPO)-dependent, erythroid cell regulatory factors secreted by endothelial cells is largely unknown. The production of thrombospondin 1 (TSP-1) and insulin-like growth factor binding protein 3 (IGFBP-3) is increased in cultures of human umbilical vein endothelial cells (HUVEC) incubated with erythropoietin (EPO). Simultaneous incubation of HUVEC with EPO and interleukin 3 (IL-3) resulted in a decreased production, suggesting that both TSP-1 and IGFBP-3 belong to the EPO- and IL-3-dependent erythroid regulatory factors previously described in cultures of bone marrow endothelial cells. TSP-1 and TSP-1 derived synthetic peptides based on the CD36 and CD47 binding sites of TSPs increased thymidine incorporation into bovine erythroid cells of fetal liver. IGBBP-3 inhibited thymidine incorporation in the same cells. Preincubation of erythroid cells with TSP-1 eliminated the inhibitory activity of IGFBP-3. We suggest that EPO-dependent, endothelial-derived TSP-1 may play a positive role in red cell production by acting directly on erythroid cells, stimulating DNA synthesis and preventing the inhibitory action of IGFBP-3.
Congote
Luis F
LF
Endocrine Laboratory, Rm. L2.05, McGill University Health Centre, 687 avenue des pins, ouest Montreal, QC, Canada H3A 1A1. luis.f.congote@muhc.mcgill.ca
DiFalco
Marcos R
MR
Gibbs
Bernard F
BF
D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D041905:Erythroid Cells / Q000187:drug effects / Q000378:metabolism*; D004921:Erythropoietin / Q000494:pharmacology*; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007377:Interleukin-3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D019700:Thrombospondin 1 / Q000378:metabolism* / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism*; D014470:Umbilical Cord / Q000187:drug effects / Q000378:metabolism*
D018972:Insulin-Like Growth Factor Binding Protein 3; D007377:Interleukin-3; D010446:Peptide Fragments; D019700:Thrombospondin 1; D004921:Erythropoietin; D013936:Thymidine