Upregulation of leukemia inhibitory factor (LIF) during the early stage of optic nerve regeneration in zebrafish.
Upregulation of leukemia inhibitory factor (LIF) during the early stage of optic nerve regeneration in zebrafish.
复制标题
斑马鱼视神经再生的早期，白血病抑制因子（LIF）的上调。
DOI：
10.1371/journal.pone.0106010
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Kato S
中科院分区：
文献类型：
--
作者：
Ogai K;Kuwana A;Hisano S;Nagashima M;Koriyama Y;Sugitani K;Mawatari K;Nakashima H;Kato S
鱼类视网膜神经节细胞(RGC)可以在视神经损伤后再生轴突，而哺乳动物RGC通常不能这样做。白介素6(IL-6)类细胞因子参与细胞的分化、增殖、存活和轴突再生，可能在斑马鱼视网膜节细胞损伤后的再生中发挥作用。在这项研究中，我们检测了IL-6型细胞因子的表达，发现其中之一，白血病抑制因子(LIF)，在斑马鱼视网膜节细胞损伤后3天上调。然后，我们展示了信号转导和转录激活因子3(STAT3)的激活，它是LIF的下游靶标，在3-5dpi。为了确定LIF的功能，我们用LIF特异的反义吗啉寡核苷酸(LIF MO)进行了LIF基因敲除实验。将LiF-MOS通过切断的视神经导入斑马鱼视网膜节细胞，可降低损伤后视网膜节细胞中LIF的表达，并抑制STAT3的激活。这些结果表明，在斑马鱼神经损伤后，上调的LIF驱动Janus Kinase(JAK)/STAT3信号转导。此外，LIF基因敲除抑制了体外培养的视网膜组织中轴突的萌发，减少了再生相关分子生长相关蛋白43(GAP-43)的表达，并延缓了体内视神经损伤后的功能恢复。在这项研究中，我们全面展示了LIF在成年斑马鱼视神经再生和功能恢复中的有益作用。
Fish retinal ganglion cells (RGCs) can regenerate their axons after optic nerve injury, whereas mammalian RGCs normally fail to do so. Interleukin 6 (IL-6)-type cytokines are involved in cell differentiation, proliferation, survival, and axon regrowth; thus, they may play a role in the regeneration of zebrafish RGCs after injury. In this study, we assessed the expression of IL-6-type cytokines and found that one of them, leukemia inhibitory factor (LIF), is upregulated in zebrafish RGCs at 3 days post-injury (dpi). We then demonstrated the activation of signal transducer and activator of transcription 3 (STAT3), a downstream target of LIF, at 3–5 dpi. To determine the function of LIF, we performed a LIF knockdown experiment using LIF-specific antisense morpholino oligonucleotides (LIF MOs). LIF MOs, which were introduced into zebrafish RGCs via a severed optic nerve, reduced the expression of LIF and abrogated the activation of STAT3 in RGCs after injury. These results suggest that upregulated LIF drives Janus kinase (Jak)/STAT3 signaling in zebrafish RGCs after nerve injury. In addition, the LIF knockdown impaired axon sprouting in retinal explant culture in vitro; reduced the expression of a regeneration-associated molecule, growth-associated protein 43 (GAP-43); and delayed functional recovery after optic nerve injury in vivo. In this study, we comprehensively demonstrate the beneficial role of LIF in optic nerve regeneration and functional recovery in adult zebrafish.
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影响因子：
5.3
作者：
ATTARDI, DG;SPERRY, RW
通讯作者：
SPERRY, RW
影响因子：
2.5
作者：
Lee, N;Neitzel, KL;MacLennan, AJ
通讯作者：
MacLennan, AJ
影响因子：
3.4
作者：
Kassen, Sean C.;Thummel, Ryan;Hyde, David R.
通讯作者：
Hyde, David R.
影响因子：
2.9
作者：
Kaneda, Manabu;Nagashima, Mikiko;Kato, Satoru
通讯作者：
Kato, Satoru
影响因子：
2.9
作者：
Hanington, Patrick C.;Belosevic, Miodrag
通讯作者：
Belosevic, Miodrag