Hepatocyte growth factor as a hematopoietic regulator.
Hepatocyte growth factor (HGF) was originally isolated as a mitogen for adult hepatocytes, but this cytokine is now regarded as a multi-functional factor. In the present study, we show that the mouse liver in the middle and/or late stage of the fetal life expresses both HGF and c-met (its receptor) messages. HGF and c-met mRNA are coexpressed not only in the adherent layers of fetal liver long-term cultures (FL-LTCs) and adult bone marrow long-term cultures (BM-LTCs), but also in the stromal cell lines MS-5 and PA-6. Addition of human HGF (2 and 20 ng/mL) to the LTCs enhances (1) nonadherent cell counts (ninefold in FL-LTCs and sixfold in BM-LTCs), (2) nonadherent colony-forming unit-in culture (CFU-C) counts (eightfold in FL-LTCs and fivefold in BM-LTC), and (3) cobblestone colony counts. However, HGF slightly inhibits the proliferation of stromal cells. No direct effect of HGF on freshly isolated BM and/or FL cells is found in the CFU-C assay. However, an approximately 1.5-fold synergistic increase in CFU-C counts is noted when the BM or FL cells are cocultured with HGF in the presence of interleukin-3. These findings strongly suggest that HGF plays a crucial role as a hematopoietic regulator in the proliferation and differentiation of hematopoietic progenitors.
Nishino
T
T
Cellular Technology Institute, Otsuka Pharmaceutical Co, Ltd, Tokushima, Japan.
Hisha
H
H
Nishino
N
N
Adachi
M
M
Ikehara
S
S
D000818:Animals; D001854:Bone Marrow Cells; D002448:Cell Adhesion; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D003238:Connective Tissue / Q000187:drug effects; D003239:Connective Tissue Cells; D018507:Gene Expression Regulation, Developmental; D005865:Gestational Age; D006410:Hematopoiesis / Q000187:drug effects; D006411:Hematopoiesis, Extramedullary / Q000502:physiology*; D016298:Hematopoietic Cell Growth Factors / Q000096:biosynthesis / Q000235:genetics; D017228:Hepatocyte Growth Factor / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D008099:Liver / Q000196:embryology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009928:Organ Specificity; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics; D019009:Proto-Oncogene Proteins c-kit; D019859:Proto-Oncogene Proteins c-met; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D016184:Receptors, Colony-Stimulating Factor / Q000096:biosynthesis / Q000235:genetics; D019089:Stem Cell Factor
D016298:Hematopoietic Cell Growth Factors; D011518:Proto-Oncogene Proteins; D016184:Receptors, Colony-Stimulating Factor; D019089:Stem Cell Factor; D017228:Hepatocyte Growth Factor; D019009:Proto-Oncogene Proteins c-kit; D019859:Proto-Oncogene Proteins c-met; D020794:Receptor Protein-Tyrosine Kinases