SOCS3 缺失促进体内视神经再生。
SOCS3 deletion promotes optic nerve regeneration in vivo.
机构信息
F.M. Kirby Neurobiology Center, Children's Hospital, and Department of Neurology, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
出版信息
Neuron. 2009 Dec 10;64(5):617-23. doi: 10.1016/j.neuron.2009.11.021.
Axon regeneration failure accounts for permanent functional deficits following CNS injury in adult mammals. However, the underlying mechanisms remain elusive. In analyzing axon regeneration in different mutant mouse lines, we discovered that deletion of suppressor of cytokine signaling 3 (SOCS3) in adult retinal ganglion cells (RGCs) promotes robust regeneration of injured optic nerve axons. This regeneration-promoting effect is efficiently blocked in SOCS3-gp130 double-knockout mice, suggesting that SOCS3 deletion promotes axon regeneration via a gp130-dependent pathway. Consistently, a transient upregulation of ciliary neurotrophic factor (CNTF) was observed within the retina following optic nerve injury. Intravitreal application of CNTF further enhances axon regeneration from SOCS3-deleted RGCs. Together, our results suggest that compromised responsiveness to injury-induced growth factors in mature neurons contributes significantly to regeneration failure. Thus, developing strategies to modulate negative signaling regulators may be an efficient strategy of promoting axon regeneration after CNS injury.
轴突再生失败是成年哺乳动物中枢神经系统损伤后导致永久性功能缺陷的原因。然而，其潜在机制仍难以捉摸。在分析不同突变体小鼠系中的轴突再生时，我们发现成年视网膜神经节细胞（RGC）中抑制细胞因子信号转导 3（SOCS3）的缺失促进了损伤视神经轴突的强烈再生。在 SOCS3-gp130 双重敲除小鼠中，这种促进再生的作用被有效地阻断，这表明 SOCS3 的缺失通过 gp130 依赖性途径促进轴突再生。一致地，视神经损伤后在视网膜内观察到睫状神经营养因子（CNTF）的短暂上调。CNTF 的玻璃体内应用进一步增强了 SOCS3 缺失的 RGC 中的轴突再生。总之，我们的结果表明，成熟神经元对损伤诱导的生长因子反应能力受损，这对再生失败有重要贡献。因此，开发调节负信号调节剂的策略可能是促进中枢神经系统损伤后轴突再生的有效策略。
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