Department of Neuroscience and Physiology, State University of New York-Upstate Medical University, Syracuse NY 13210, USA.
Exp Neurol. 2010 Sep;225(1):123-32. doi: 10.1016/j.expneurol.2010.06.002. Epub 2010 Jun 12.
Transforming growth factor (TGF) beta1 is a key player in early brain development, hence, its availability (i.e., synthesis and release) affects neuronogenesis. TGFbeta1 moves proliferating cells out of the cell cycle and promotes their subsequent migration. The present study tested the hypothesis that neural progenitors self-regulate TGFbeta1. B104 neuroblastoma cells which can grow in the absence of serum or growth factors were used in systematic studies of transcription, translation, release, and activation. These studies relied on quantitative enzyme-linked immunosorbent assays and real-time polymerase chain reactions. TGFbeta1 positively upregulated its own intracellular expression and promoted increased release of TGFbeta1 from cells. The induction of TGFbeta1 was independent of a change in transcription, but it depended on cycloheximide-inhibited translation. Signaling mediated by downstream Smad2/3 through the TGFbeta receptors and intracellular protein transport were also required for release of TGFbeta1 from B104 cells. Thus, TGFbeta1 production and release were mediated through a feed-forward mechanism and were pivotally regulated at the level of translation. These activities appear to be key for the role of TGFbeta1 in the proliferation and migration of young neurons.
转化生长因子 (TGF) beta1 是大脑早期发育的关键因子，因此其可用性（即合成和释放）会影响神经元发生。TGFbeta1 可使增殖细胞退出细胞周期并促进其随后的迁移。本研究检验了神经祖细胞自我调节 TGFbeta1 的假设。B104 神经母细胞瘤细胞可以在没有血清或生长因子的情况下生长，用于对转录、翻译、释放和激活进行系统研究。这些研究依赖于定量酶联免疫吸附测定和实时聚合酶链反应。TGFbeta1 可正向上调其自身的细胞内表达，并促进 TGFbeta1 从细胞中释放增加。TGFbeta1 的诱导不依赖于转录的变化，但依赖于环己酰亚胺抑制的翻译。通过 TGFbeta 受体和细胞内蛋白质转运介导的下游 Smad2/3 信号传导对于 B104 细胞中 TGFbeta1 的释放也是必需的。因此，TGFbeta1 的产生和释放是通过正反馈机制介导的，并且在翻译水平上受到关键调节。这些活动似乎对于 TGFbeta1 在年轻神经元的增殖和迁移中的作用至关重要。
