The Key Laboratory of Gene Engineering of Education Ministry, Zhongshan University, Guangzhou, 510275, People's Republic of China.
Int J Hematol. 2011 Jul;94(1):44-53. doi: 10.1007/s12185-011-0828-5. Epub 2011 Jun 7.
The human homolog of a fungal nuclear migration protein (hNUDC) has recently been shown in in vitro studies to overlap in function with the cytokine factor thrombopoietin (TPO) in its ability to induce human megakaryocyte development. In the present study, we sought to confirm the hypothesis that combination of TPO and NUDC may result in additive or synergistic effects on megakaryocyte maturation in bone marrow. For this purpose, murine bone marrow cells were stimulated with murine NUDC (mNUDC), either alone or in conjunction with murine thrombopoietin (mTPO), in serum-free medium. Studies showed that mNUDC + mTPO treatments resulted in the greatest number of colony-forming unit of megakaryocytes. Concomitantly, mNUDC + mTPO enhanced expression of CD61 and elicited the largest number of megakaryocytes, with higher ploidy and larger size. In addition, in vivo experiments revealed an elevation of platelet levels in normal and thrombocytopenic mice that had been administered mTPO + mNUDC. Moreover, mRNA levels of mNUDC and murine thrombopoietin receptor were much higher than the levels of mTPO mRNA at two different phases of normal murine megakaryocyte maturation. Furthermore, levels of ERK1/2 and Akt phosphorylation are higher with mNUDC in combination with mTPO. This study demonstrates that the combination of mTPO and mNUDC provides additive induction of megakaryocyte maturation in vitro and platelet production in vivo.
在体外研究中，最近发现真菌核迁移蛋白（hNUDC）的人类同源物在功能上与细胞因子因子血小板生成素（TPO）重叠，能够诱导人类巨核细胞的发育。在本研究中，我们试图证实这样一种假设，即 TPO 和 NUDC 的组合可能导致骨髓中巨核细胞成熟的附加或协同作用。为此，我们在无血清培养基中用鼠类 NUDC（mNUDC）刺激鼠类骨髓细胞，单独或与鼠类血小板生成素（mTPO）一起刺激。研究表明，mNUDC + mTPO 处理导致集落形成单位的巨核细胞数量最多。同时，mNUDC + mTPO 增强了 CD61 的表达，并引发了最多数量的巨核细胞，具有更高的倍性和更大的体积。此外，体内实验显示，给予 mTPO + mNUDC 的正常和血小板减少小鼠的血小板水平升高。此外，在正常和血小板减少的小鼠的巨核细胞成熟的两个不同阶段，mNUDC 和鼠类血小板生成素受体的 mRNA 水平远高于 mTPO mRNA 水平。此外，ERK1/2 和 Akt 磷酸化水平在 mNUDC 与 mTPO 结合时更高。这项研究表明，mTPO 和 mNUDC 的组合在体外提供了巨核细胞成熟和体内血小板生成的附加诱导。
