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

^a First Department of Pathology,
^b Department of Hygiene,
^c Department of Pediatrics,
^d First Department of Internal Medicine, Kansai Medical University, Moriguchi City, Osaka, Japan;
^e Cellular Technology Institute, Otsuka Pharmaceutical Co. Ltd., Tokushima, Japan;
^f Laboratory of Biosignals and Response, Division of Applied Sciences, Graduate School of Agriculture, Kyoto University, Kyoto, Japan

Key Words. HGF • Human cord blood • Signal transduction • Erythropoiesis

Correspondence: Dr. Susumu Ikehara, First Department of Pathology, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi City, Osaka 570-8506, Japan.

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.

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