Division of Neuroanatomy, Innsbruck Medical University, Muellerstrasse 59, A-6020 Innsbruck, Austria.
Mol Cell Neurosci. 2009 Dec;42(4):328-40. doi: 10.1016/j.mcn.2009.08.005. Epub 2009 Aug 14.
Fibroblast growth factors (FGFs) play a prominent role in axonal growth during development and repair. Treatment with FGF-2 or overexpression of FGF receptors promotes peripheral axon regeneration mainly by activation of extracellular signal-regulated kinase (ERK). The Ras/Raf/ERK pathway is under the control of Sprouty proteins acting as negative feedback inhibitors. We investigated the expression of Sprouty isoforms in adult sensory neurons of dorsal root ganglia (DRG) as well as the effects of Sprouty inhibition on axon growth by small interfering RNAs (siRNAs). Sprouty2 revealed the highest expression level in DRG neurons. Down-regulation of Sprouty2 promoted elongative axon growth by adult sensory neurons accompanied by enhanced FGF-2-induced activation of ERK and Ras, whereas Sprouty2 overexpression inhibited axon growth. Sprouty2 was not regulated in vivo in response to a sciatic nerve lesion. Together, our results imply that Sprouty2 is highly expressed in adult peripheral neurons and its down-regulation strongly promotes elongative axon growth by activation of the Ras/Raf/ERK pathway.
成纤维细胞生长因子（FGFs）在发育和修复过程中的轴突生长中起着重要作用。用 FGF-2 治疗或过表达 FGF 受体主要通过激活细胞外信号调节激酶（ERK）促进周围轴突再生。Ras/Raf/ERK 途径受 Sprouty 蛋白的控制，Sprouty 蛋白作为负反馈抑制剂发挥作用。我们研究了 Sprouty 同种型在背根神经节（DRG）成年感觉神经元中的表达，以及通过小干扰 RNA（siRNA）抑制 Sprouty 对轴突生长的影响。Sprouty2 在 DRG 神经元中表达水平最高。下调 Sprouty2 促进成年感觉神经元的轴突伸长生长，同时增强 FGF-2 诱导的 ERK 和 Ras 的激活，而 Sprouty2 的过表达则抑制轴突生长。Sprouty2 没有在体内受到坐骨神经损伤的调节。总之，我们的研究结果表明，Sprouty2 在成年周围神经元中高度表达，其下调通过激活 Ras/Raf/ERK 途径强烈促进轴突伸长生长。
