期刊
BLOOD
卷 137, 期 11, 页码 1457-1467出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood.2020007172
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- Japan Science and Technology Agency (PRESTO) [JPMJPR12M7]
- Japan Agency for Medical Research (AMED) (CREST) [JP18gm0910012h2]
- Japan Society for the Promotion of Science [15H04856, 18H02837, 17K19660]
- Grants-in-Aid for Scientific Research [17K19660, 18H02837, 15H04856] Funding Source: KAKEN
FGF-23, produced by erythroblasts, plays a crucial role in G-CSF-induced hematopoietic progenitor cell mobilization by inhibiting chemoattraction, facilitating the release of HPCs from bone marrow into circulation.
Fibroblast growth factor 23 (FGF-23) hormone is produced by bone-embedded osteocytes and regulates phosphate homeostasis in kidneys. We found that administration of granulocyte colony-stimulating factor (G-CSF) to mice induced a rapid, substantial increase in FGF-23 messenger RNA in bone marrow (BM) cells. This increase originated mainly from CD452Ter1191CD711 erythroblasts. FGF-23 protein in BM extracellular fluid was markedly increased during G-CSF-induced hematopoietic progenitor cell (HPC) mobilization, but remained stable in the blood, with no change in the phosphate level. Consistent with the BM hypoxia induced by G-CSF, low oxygen concentration induced FGF-23 release from human erythroblast HUDEP-2 cells in vitro. The efficient mobilization induced by G-CSF decreased drastically in both FGF-232/2 and chimeric mice with FGF-23 deficiency, only in hematopoietic cells, but increased in osteocyte-specific FGF-232/2 mice. This finding suggests that erythroblast-derived, but not bone-derived, FGF-23 is needed to release HPCs from BM into the circulation. Mechanistically, FGF-23 did not influence CXCL-12 binding to CXCR-4 on progenitors but interfered with their transwell migration toward CXCL-12, which was canceled by FGF receptor inhibitors. These results suggest that BM erythroblasts facilitate G-CSF-induced HPC mobilization via FGF-23 production as an intrinsic suppressor of chemoattraction.
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