HGF activates signal transduction from EPO receptor on human cord blood CD34(+)/CD45(+) cells

Hepatocyte growth factor (HGF) is a multifunctional cytokine with early hem atopoiesis-stimulatory activity. Here, we focus on its erythropoiesis-stimu latory 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 t he CD34(+)/CD45(+) cells, although the expression levels were different amo ng 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 expressio n level had been low, IL-6, G-CSF, or erythropoietin (EPO) did not show suc h a stimulatory effect on the c-met expression of the cells. When HGF was a dded to the CD34(+)/CD45(+) cells in the presence of SCF, the numbers of CD 36(+)/CD11b(-) cells (very early erythroid lineage cells) and BFU-E increas ed. EPO-dependent tyrosine phosphorylation of Stat 5 also increased, but th e 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 S CF, The subsequent enhancement of signal transduction via the activation of Stat 5 from the EPO-R plays a crucial role in the commitment of hematopoie tic stem cells into erythroid lineage cells.