Brazel C Y, Ducceschi M H, Pytowski B, Levison S W
Department of Neuroscience and Anatomy, Penn State University College of Medicine, Hershey, Pennsylvania 17033, USA.
Mol Cell Neurosci. 2001 Oct;18(4):381-93. doi: 10.1006/mcne.2001.1033.
The FLT3 receptor tyrosine kinase (FLT3) was originally identified on hematopoietic stem cells (HSCs) and its ligand (FL) induces HSC proliferation. As stem cells originating from various tissues are more similar than once thought, the goal of this study was to determine whether neural stem cells express FLT3 and proliferate in response to FL. In fact, a subset of neural stem/progenitor cells does express FLT3, but contrary to our expectations, FL inhibited EGF and FGF-2 stimulated proliferation. Since FLT3 is expressed weakly by proliferative neuroepithelia but strongly by subsets of neurons in the CNS and PNS, we tested its ability to support neuronal survival. FL synergized with NGF to promote the survival of cultured DRG neurons, although it lacked any neurotrophic activity alone. We conclude that FL serves as an adjunct trophic factor in the nervous system, which differs from its role in the hematopoietic system.
FMS样酪氨酸激酶3受体酪氨酸激酶（FLT3）最初是在造血干细胞（HSC）上被鉴定出来的，其配体（FL）可诱导造血干细胞增殖。由于源自各种组织的干细胞比以往认为的更为相似，本研究的目的是确定神经干细胞是否表达FLT3，并对FL作出增殖反应。事实上，神经干/祖细胞的一个亚群确实表达FLT3，但与我们的预期相反，FL抑制了表皮生长因子（EGF）和碱性成纤维细胞生长因子2（FGF-2）刺激的增殖。由于FLT3在增殖性神经上皮中表达较弱，但在中枢神经系统（CNS）和周围神经系统（PNS）的神经元亚群中表达较强，我们测试了其支持神经元存活的能力。FL与神经生长因子（NGF）协同作用，促进培养的背根神经节（DRG）神经元的存活，尽管它单独缺乏任何神经营养活性。我们得出结论，FL在神经系统中作为一种辅助营养因子发挥作用，这与其在造血系统中的作用不同。
