SOCS3 deletion promotes optic nerve regeneration in vivo.
SOCS3 deletion promotes optic nerve regeneration in vivo.
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DOI：
10.1016/j.neuron.2009.11.021
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发表时间：
2009-12-10
期刊：
影响因子：
16.2
通讯作者：
He, Zhigang
中科院分区：
文献类型：
--
作者：
Smith, Patrice D.;Sun, Fang;Park, Kevin Kyungsuk;Cai, Bin;Wang, Chen;Kuwako, Kenichiro;Martinez-Carrasco, Irene;Connolly, Lauren;He, Zhigang
成年哺乳动物中枢神经系统损伤后轴突再生障碍是永久性的功能缺陷。然而，根本的机制仍然难以捉摸。在分析不同突变小鼠系中的轴突再生时，我们发现在成年视网膜神经节细胞（RGC）中细胞因子信号传导抑制因子3（SOCS 3）的缺失促进受损视神经轴突的稳健再生。这种再生促进作用在SOCS 3-gp 130双敲除小鼠中被有效阻断，表明SOCS 3缺失通过gp 130依赖性途径促进轴突再生。结论：视神经损伤后，睫状神经营养因子（CNTF）在视网膜内表达上调。CNTF的玻璃体内应用进一步增强了SOCS 3缺失的RGCs的轴突再生。总之，我们的研究结果表明，受损的反应损伤诱导的生长因子在成熟的神经元再生失败显着贡献。因此，开发调节负信号调节剂的策略可能是促进CNS损伤后轴突再生的有效策略。
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 up-regulation 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.
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