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Stimulation of thrombopoiesis in mice by fibroblast growth factor 9
S Matsumoto-Yoshitomi1, C Seko, K Kuroshima
1Department II, Takeda Chemical Industries Ltd, Osaka, Japan.
Abstract:
Fibroblast growth factor 9 (FGF-9), a novel member of the FGF family, was found to have thrombopoietic activity in vitro and in vivo. In an in vitro megakaryocyte colony-stimulating factor assay, anti-mouse interleukin-6 (IL-6) monoclonal antibody neutralized FGF-9 activity. This suggests that the activity may be exerted via IL-6 induction. BALB/c mice that received subcutaneous FGF-9 injections of 4 to 100 micrograms/day for 2 weeks showed a dose-dependent transient increase in peripheral platelet counts 10 to 12 days after the first treatment. Histologic studies showed a marked increase in megakaryocytes in bone marrow and extramedullary hematopoiesis in the spleen and the liver. Examination of changes in the DNA content of bone marrow megakaryocytes revealed that the ploidy distribution underwent a marked shift 3 days after FGF-9 injection, with a large increase in the 2N megakaryocyte population. The major modal ploidy shifted from the normal 16N to 2N. The number of megakaryocyte progenitor cells in FGF-9-treated mice increased up to 1.5-fold in the bone marrow and 10-fold in the spleen on day 6. These results indicate that FGF-9 acts on the in vivo proliferation of megakaryocytes.
Insights
Fibroblast growth factor 9 (FGF-9) stimulates platelet production by increasing megakaryocytes in bone marrow and spleen. This thrombopoietic activity may involve interleukin-6 (IL-6) induction, impacting megakaryocyte proliferation and ploidy.
Area of Science:
- Hematology
- Molecular Biology
- Cell Biology
Background:
- Fibroblast growth factor 9 (FGF-9) is a novel member of the FGF family.
- FGF-9 has demonstrated thrombopoietic activity in preliminary studies.
Purpose of the Study:
- To investigate the thrombopoietic activity of FGF-9 in vitro and in vivo.
- To elucidate the mechanism underlying FGF-9's effect on platelet production.
Main Methods:
- In vitro megakaryocyte colony-stimulating factor assay with anti-IL-6 antibody.
- Subcutaneous FGF-9 injections in BALB/c mice.
- Peripheral platelet counts, bone marrow histology, spleen and liver examination.
- Analysis of megakaryocyte DNA content and ploidy distribution.
- Quantification of megakaryocyte progenitor cells.
Main Results:
- FGF-9 induced a dose-dependent increase in peripheral platelet counts in mice.
- Histologic studies revealed increased megakaryocytes in bone marrow and extramedullary hematopoiesis.
- FGF-9 injection caused a shift in megakaryocyte ploidy distribution towards the 2N population.
- Significant increases in megakaryocyte progenitor cells were observed in bone marrow and spleen.
Conclusions:
- FGF-9 exhibits significant thrombopoietic activity in vivo.
- FGF-9's action appears to involve IL-6 induction and impacts megakaryocyte proliferation and ploidy.
- FGF-9 is a potential therapeutic agent for platelet-related disorders.