Upregulation of IGF-I in the goldfish retinal ganglion cells during the early stage of optic nerve regeneration
Upregulation of IGF-I in the goldfish retinal ganglion cells during the early stage of optic nerve regeneration
复制标题
DOI：
10.1016/j.neuint.2007.01.012
复制
发表时间：
2007-04-01
影响因子：
4.2
通讯作者：
Kato, Satoru
中科院分区：
文献类型：
--
作者：
Koriyama, Yoshiki;Homma, Keiko;Kato, Satoru
视神经损伤后金鱼视网膜神经节细胞（RGCs）可再生轴突。然而，在分子水平上，金鱼RGCs在神经损伤后能够再生的原因在很大程度上是未知的。为了研究金鱼RGC的再生特性，我们将RGC再生过程分为两个部分：(1)RGC存活过程和(2)轴突伸长过程。为了表征视神经损伤后RGC存活信号通路，我们研究了金鱼视网膜中Bcl-2家族成员等细胞存活/死亡信号。在神经损伤后3-5天，金鱼视网膜中磷酸化- akt （p-Akt）和磷酸化- bad （p-Bad）的蛋白水平迅速增加4 -5倍。随后，Bcl-2水平增加1.7倍，损伤后10-20天caspase-3活性略有下降。此外，激活磷脂酰肌醇-3激酶(PI3K)/Akt系统的胰岛素样生长因子- i （IGF-I）水平在金鱼视网膜中比p-Akt提前2-3天升高。这些分子变化的细胞定位仅限于rgc。IGF-I处理显著诱导Akt磷酸化，并显著诱导金鱼视网膜神经突生长。相反，在外植体培养中，添加PI3K抑制剂wortmannin和IGF-I抗体可抑制Akt磷酸化和神经突生长。因此，我们首次证明了IGF-I早期上调的信号级联，通过PI3K/ Akt系统导致视神经损伤后成年金鱼视网膜RGC存活和轴突再生。目前的数据有力地表明，igf - 1是控制视神经损伤后RGCs再生的重要分子之一。(c) 2007 Elsevier Ltd.版权所有。
Goldfish retinal ganglion cells (RGCs) can regrow their axons after optic nerve injury. However, the reason why goldfish RGCs can regenerate after nerve injury is largely unknown at the molecular level. To investigate regenerative properties of goldfish RGCs, we divided the RGC regeneration process into two components: (1) RGC survival, and (2) axonal elongation processes. To characterize the RGC survival signaling pathway after optic nerve injury, we investigated cell survival/death signals such as Bcl-2 family members in the goldfish retina. Amounts of phospho-Akt (p-Akt) and phospho-Bad (p-Bad) in the goldfish retina rapidly increased four- to five-fold at the protein level by 3-5 days after nerve injury. Subsequently, Bcl-2 levels increased 1.7-fold, accompanied by a slight reduction in caspase-3 activity 10-20 days after injury. Furthermore, level of insulin-like growth factor-I (IGF-I), which activates the phosphatidyl inositol-3-kinase (PI3K)/Akt system, increased 2-3 days earlier than that of p-Akt in the goldfish retina. The cellular localization of these molecular changes was limited to RGCs. IGF-I treatment significantly induced phosphorylation of Akt, and strikingly induced neurite outgrowth in the goldfish retina in vitro. On the contrary, addition of the PI3K inhibitor wortmannin, and IGF-I antibody inhibited Akt phosphorylation and neurite outgrowth in an explant culture. Thus, we demonstrated, for the first time, the signal cascade for early upregulation of IGF-I, leading to RGC survival and axonal regeneration in adult goldfish retinas through PI3K/ Akt system after optic nerve injury. The present data strongly indicate that IGF-I is one of the most important molecules for controlling regeneration of RGCs after optic nerve injury. (c) 2007 Elsevier Ltd. All rights reserved.