Effect of nerve growth factor on erythropoiesis in mice and its underlying mechanism

This study was aimed to explore the effect of nerve growth factor (NGF) on erythropoiesis and to elucidate the underlying mechanism. Using flow cytometry, colony forming assay, blood cell counter, fluorescent real-time quantitation PCR, and enzyme-linked immunosorbent assay (ELISA), the changes in the bone marrow cells (BMCs) proliferation cycle, CFU-E and BFU-E counts, the peripheral blood erythroid related parameters, kidney EPO, BMC GM-CSF, spleen EPO receptor (EPOR) mRNA expression, and serum EPO, GM-CSF, and IL-1 concentrations were all determined after NGF was injected intramuscularly into the thigh of mice, meanwhile the change of BFU-E and CFU-E counts and its relationship with EPO, IL-3 were investigated. The results indicated that the cell proportion in S+G2/M phase, the CFU-E and BFU-E counts of BMCs and the spleen EPOR mRNA expression in injection of NGF (7.5 microg/kg) for 7 days were significantly higher than that in injection of physiological saline for 13-19 days; red blood cell, hemoglobin, and reticulocyte counts increased as well. In vitro, NGF stimulated a dose-dependent increase of CFU-E colonies formation in the semisolid culture system with or without exogenous EPO; the colony counts in the system with NGF alone were significantly higher than that in the system with exogenous EPO alone. The BFU-E counts in the system with exogenous NGF and IL-3 were significantly higher than that in the system with exogenous EPO and IL-3. It is concluded that the NGF promotes the responsibility of hematopoietic cells to EPO and activates the same signal transduction pathway as EPO in hematopoietic cells, and then accelerates the BMCs into mitosis, the HSCs differentiating into erythroid cells, and CFU-E and BFU-E formation.