期刊
INTERNATIONAL JOURNAL OF HEMATOLOGY
卷 101, 期 1, 页码 5-12出版社
SPRINGER JAPAN KK
DOI: 10.1007/s12185-014-1690-z
关键词
Cell division control protein 42 homolog; Hematopoietic stem and progenitor cell; Granulocyte colony-stimulating factor; Mobilization; Mouse
类别
资金
- National Natural Science Foundation of China [81000210, 81471580, 81200376, 81272206, 81270637, 81370671]
- Jiangsu Special Grant of Clinical Science [BL2012022, BL2013010]
G-CSF is the most often used agent in clinical hematopoietic stem and progenitor cell (HSPC) mobilization. However, in about 10 % of patients, G-CSF does not efficiently mobilize HSPC in clinically sufficient amounts. Cdc42 activity is involved in HSPC mobilization. In the present study, we explore the impact of Cdc42 inhibitor ML141 on G-CSF-mediated HSPC mobilization in mice. We found that the use of ML141 alone only triggered modest HSPC mobilization effect in mice. However, combination of G-CSF and ML141 significantly promoted HPSC counts and colony forming units in peripheral blood, as compared to mice treated with G-CSF alone. ML141 did not significantly alter the levels of SDF-1 and MMP-9 in the bone marrow, when used alone or in combination with G-CSF. We also found that G-CSF administration significantly increases the level of GTP-bound Cdc42, but does not alter the expression of Cdc42 in the bone marrow. Our data indicate that the Cdc42 signal is a negative regulator in G-CSF-mediated HSPC mobilization, and that inhibition of the Cdc42 signal efficiently improves mobilization efficiency. These findings may provide a new strategy for efficient HSPC mobilization, especially in patients with poor G-CSF response.
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