HGF Activates Signal Transduction from EPO Receptor on Human Cord Blood CD34+/CD45+ Cells

Hepatocyte growth factor (HGF) is a multifunctional cytokine with early hematopoiesis‐stimulatory activity. Here, we focus on its erythropoiesis‐stimulatory effect on highly purified human hematopoietic progenitor cells (CD34+/CD45+ cells) derived from the cord blood. In immunoblot analyses, c‐met protein (a receptor of HGF) was detected in the CD34+/CD45+ cells, although the expression levels were different among samples. The c‐met expression was facilitated by incubation of the cells with stem cell factor (SCF) or interleukin 3 (IL‐3), even if the expression level had been low. IL‐6, G‐CSF, or erythropoietin (EPO) did not show such a stimulatory effect on the c‐met expression of the cells. When HGF was added to the CD34+/CD45+ cells in the presence of SCF, the numbers of CD36+/CD11b− cells (very early erythroid lineage cells) and BFU‐E increased. EPO‐dependent tyrosine phosphorylation of Stat 5 also increased, but the EPO receptor (EPO‐R) expression remained unchanged in the CD34+/CD45+ cells treated with SCF + HGF. Our present study suggests that stimulation of the HGF/c‐met signal is concomitant with induction of c‐met protein by SCF. The subsequent enhancement of signal transduction via the activation of Stat 5 from the EPO‐R plays a crucial role in the commitment of hematopoietic stem cells into erythroid lineage cells.