Open AccessHGF Activates Signal Transduction from EPO Receptor on Human Cord Blood CD34 + /CD45 + Cells
Author(s) -
Iguchi Tomoko,
Sogo Shinji,
Hisha Hiroko,
Taketani Shigeru,
Adachi Yasushi,
Miyazaki Rika,
Ogata Hajime,
Masuda Seiji,
Sasaki Ryuzo,
Ito Motoki,
Fukuhara Shirou,
Ikehara Susumu
Publication year - 1999
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.170082
Subject(s) - stem cell factor , biology , hepatocyte growth factor , erythropoietin , haematopoiesis , cord blood , cd34 , interleukin 3 , erythropoietin receptor , progenitor cell , stem cell , signal transduction , microbiology and biotechnology , cytokine , hematopoietic growth factor , receptor , endocrinology , immunology , t cell , immune system , antigen presenting cell , biochemistry
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.