JUN regulates early transcriptional responses to axonal injury in retinal ganglion cells.
JUN regulates early transcriptional responses to axonal injury in retinal ganglion cells.
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DOI：
10.1016/j.exer.2013.04.021
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发表时间：
2013-07
影响因子：
3.4
通讯作者：
Libby, Richard T.
中科院分区：
文献类型：
--
作者：
Fernandes, Kimberly A.;Harder, Jeffrey M.;Kim, Jessica;Libby, Richard T.
AP1家族转录因子JUN是神经元对损伤反应的重要分子。在视网膜神经节细胞（RGCs）中，JUN在轴突损伤后很快上调，破坏JUN活性可延迟RGC死亡。已知JUN参与控制神经元中许多不同的损伤反应通路，包括控制细胞死亡和轴突再生的通路。我们测试了JUN在调节细胞死亡、内质网应激和再生相关基因中的作用，以确定JUN在调节RGC对轴突损伤反应中的总体重要性。轴突损伤后，来自这些通路的基因都受到转录控制，而Jun缺乏症改变了许多这些基因的表达。差异表达基因包括：Atf3、Ddit3、Ecel1、Gadd45α、Gal、Hrk、Pten、Socs3和Sprr1a。其中两个基因，Hrk和Atf3，使用每个基因的零等位基因来测试在RGC死亡中的重要性。前驱Bcl2家族成员Hrk的破坏不影响轴突创伤后RGC死亡的发生率或数量。ATF/CREB家族转录因子Atf3的缺乏确实减少了RGC损伤后死亡的数量，尽管它没有对RGC提供长期保护。由于JUN的二聚化伙伴决定了它的转录靶点，我们检测了几个候选AP1家族成员的表达。多个AP1家族成员在轴突损伤诱导下，与野生型视网膜相比，在Jun缺陷视网膜中具有不同的表达谱（Fosl1， Fosl2和Jund）。总之，JUN似乎在调节RGC对轴索损伤的反应中发挥了多方面的作用。
The AP1 family transcription factor JUN is an important molecule in the neuronal response to injury. In retinal ganglion cells (RGCs), JUN is upregulated soon after axonal injury and disrupting JUN activity delays RGC death. JUN is known to participate in the control of many different injury response pathways in neurons, including pathways controlling cell death and axonal regeneration. The role of JUN in regulating genes involved in cell death, ER stress, and regeneration was tested to determine the overall importance of JUN in regulating RGC response to axonal injury. Genes from each of these pathways were transcriptionally controlled following axonal injury and Jun deficiency altered the expression of many of these genes. The differentially expressed genes included, Atf3, Ddit3, Ecel1, Gadd45α, Gal, Hrk, Pten, Socs3, and Sprr1a. Two of these genes, Hrk and Atf3, were tested for importance in RGC death using null alleles of each gene. Disruption of the prodeath Bcl2 family member Hrk did not affect the rate or amount of RGC death after axonal trauma. Deficiency in the ATF/CREB family transcription factor Atf3 did lessen the amount of RGC death after injury, though it did not provide long term protection to RGCs. Since JUN’s dimerization partner determines its transcriptional targets, the expression of several candidate AP1 family members were examined. Multiple AP1 family members were induced by axonal injury and had a different expression profile in Jun deficient retinas compared to wildtype retinas (Fosl1, Fosl2 and Jund). Overall, JUN appears to play a multifaceted role in regulating RGC response to axonal injury.
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影响因子：
6.1
作者：
Fernandes, Kimberly A.;Harder, Jeffrey M.;Fornarola, Laura B.;Freeman, Robert S.;Clark, Abbot F.;Pang, Iok-Hou;John, Simon W. M.;Libby, Richard T.
通讯作者：
Libby, Richard T.
影响因子：
11.4
作者：
Behrens, A;Sibilia, M;Wagner, EF
通讯作者：
Wagner, EF
影响因子：
4.6
作者：
Harder, Jeffrey M.;Fernandes, Kimberly A.;Libby, Richard T.
通讯作者：
Libby, Richard T.
影响因子：
3
作者：
Hartl, M.;Bader, A. G.;Bister, K.
通讯作者：
Bister, K.
影响因子：
3.5
作者：
Harder, Jeffrey M.;Ding, Qian;Libby, Richard T.
通讯作者：
Libby, Richard T.