Novel role of 1,25(OH)2D3 in induction of erythroid progenitor cell proliferation

Objective. Burst-forming unit erythroid and colony-forming unit erythroid growth in vitro is lower in studies of continuous ambulatory peritoneal dialysis patients than healthy controls. Burst-forming unit erythroid growth was potentiated by addition of 1alpha,25-dihydroxyvitamin D-3 [1,25(OH)(2)D-3] and normalized by erythropoietin (Epo) therapy, suggesting an interaction between Epo and 1,25(OH)(2)D-3 at the stem cell level. The objective of this study was to determine the mechanism by which 1,25(OH)(2)D-3 enhances the stimulatory effect of Epo on the growth of erythroid precursor cells. Materials and Methods. We examined the effect of 1,25(OH)(2)D-3 and Epo on stem cell proliferation. Proliferation of TF1 cells of erythroid origin was measured by the XTT method, (3)[H] thymidine incorporation, and cell counting by trypan blue exclusion; cord blood (CB) stem cells were counted. Epo receptor (EpoR) quantitation was evaluated by I-125-Epo binding and Scatchard analysis, immunoprecipitation, and Western blotting. Expression of EpoR mRNA was measured by reverse transcriptase polymerase chain reaction. Results. The stem cell factor-dependent CB stem cells and the TF1 cells responded to Epo and 1,25(OH)(2)D-3 by increased proliferation, while their simultaneous addition potentiated cell proliferation in a synergistic manner (25.67% +/- 4.8% of Epo proliferation at day 10 for CB cells; p < 0.005). 1,25(OH)(2)D-3 produced an up-regulation of EpoR number in TF1 cells and increased the expression of EpoR mRNA (p < 0.01). Conclusions. The increase in EpoR expression induced by 1,25(OH)(2)D-3 might explain the synergistic interaction between Epo and 1,25(OH)(2)D-3 in stem cells. (C) 2002 International Society for Experimental Hematology. Published by Elsevier Science Inc.