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.
Iguchi
T
T
First Department of Pathology, Kansai Medical University, Moriguchi City, Osaka, Japan.
Sogo
S
S
Hisha
H
H
Taketani
S
S
Adachi
Y
Y
Miyazaki
R
R
Ogata
H
H
Masuda
S
S
Sasaki
R
R
Ito
M
M
Fukuhara
S
S
Ikehara
S
S
D018952:Antigens, CD34 / Q000378:metabolism*; D015153:Blotting, Western; D018955:CD36 Antigens / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D005312:Fetal Blood / Q000378:metabolism*; D005434:Flow Cytometry; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006410:Hematopoiesis / Q000502:physiology; D006412:Hematopoietic Stem Cells; D017228:Hepatocyte Growth Factor / Q000502:physiology*; D006801:Humans; D007377:Interleukin-3 / Q000378:metabolism; D008894:Milk Proteins; D011233:Precipitin Tests; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D017463:Receptors, Complement 3b / Q000378:metabolism*; D017467:Receptors, Erythropoietin / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050799:STAT5 Transcription Factor; D015398:Signal Transduction; D019089:Stem Cell Factor / Q000378:metabolism; D013997:Time Factors; D015534:Trans-Activators / Q000276:immunology
D018952:Antigens, CD34; D018955:CD36 Antigens; D004268:DNA-Binding Proteins; D007377:Interleukin-3; D008894:Milk Proteins; D017463:Receptors, Complement 3b; D017467:Receptors, Erythropoietin; D050799:STAT5 Transcription Factor; D019089:Stem Cell Factor; D015534:Trans-Activators; D016179:Granulocyte Colony-Stimulating Factor; D017228:Hepatocyte Growth Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D019859:Proto-Oncogene Proteins c-met