Atf3 mutant mice show reduced axon regeneration and impaired regeneration-associated gene induction after peripheral nerve injury.
Atf3 mutant mice show reduced axon regeneration and impaired regeneration-associated gene induction after peripheral nerve injury.
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DOI：
10.1098/rsob.160091
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发表时间：
2016-08
期刊：
影响因子：
5.8
通讯作者：
Knöll B
中科院分区：
文献类型：
--
作者：
Gey M;Wanner R;Schilling C;Pedro MT;Sinske D;Knöll B
外周神经系统（PNS）轴突损伤诱导再生相关基因（RAG）反应。Atf3（激活转录因子3）就是这样一个RAG， Atf3的转录活性可能诱导“效应”RAG（如富含脯氨酸的小蛋白1a （Sprr1a）、甘丙氨酸（Gal）、生长相关蛋白43 (Gap43)）促进外周轴突再生。我们提供了Atf3小鼠周围神经再生突变体的首次分析。在Atf3突变小鼠中，面神经再生和成年Atf3缺陷原代背根神经节神经元的神经突生长减少。利用全基因组转录组学，我们鉴定了一个由ATF3调控的神经肽编码RAG簇（血管活性肠肽（Vip）、Ngf、Grp、Gal、Pacap）。外源性给药神经肽可促进Atf3突变小鼠的神经突生长，提示这些分子可能是Atf3促再生功能的效应因子。除了诱导生长促进分子外，我们还提供了ATF3抑制生长抑制分子如趋化因子（C-C基序）配体2的数据。总之，我们发现在PNS神经再生过程中，ATF3的促再生功能涉及神经肽编码RAG簇的转录激活。ATF3是一种常见的损伤诱导因子，因此本文确定的ATF3介导机制可能适用于其他细胞和损伤类型。
Axon injury in the peripheral nervous system (PNS) induces a regeneration-associated gene (RAG) response. Atf3 (activating transcription factor 3) is such a RAG and ATF3's transcriptional activity might induce ‘effector’ RAGs (e.g. small proline rich protein 1a (Sprr1a), Galanin (Gal), growth-associated protein 43 (Gap43)) facilitating peripheral axon regeneration. We provide a first analysis of Atf3 mouse mutants in peripheral nerve regeneration. In Atf3 mutant mice, facial nerve regeneration and neurite outgrowth of adult ATF3-deficient primary dorsal root ganglia neurons was decreased. Using genome-wide transcriptomics, we identified a neuropeptide-encoding RAG cluster (vasoactive intestinal peptide (Vip), Ngf, Grp, Gal, Pacap) regulated by ATF3. Exogenous administration of neuropeptides enhanced neurite growth of Atf3 mutant mice suggesting that these molecules might be effector RAGs of ATF3's pro-regenerative function. In addition to the induction of growth-promoting molecules, we present data that ATF3 suppresses growth-inhibiting molecules such as chemokine (C-C motif) ligand 2. In summary, we show a pro-regenerative ATF3 function during PNS nerve regeneration involving transcriptional activation of a neuropeptide-encoding RAG cluster. ATF3 is a general injury-inducible factor, therefore ATF3-mediated mechanisms identified herein might apply to other cell and injury types.
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影响因子：
5.3
作者：
Jing, Xiaotang;Wang, Ting;Huang, Shaohua;Glorioso, Joseph C.;Albers, Kathryn M.
通讯作者：
Albers, Kathryn M.
DOI：
10.1083/jcb.201205025
发表时间：
2012-07-09
期刊：
The Journal of cell biology
影响因子：
--
作者：
Fontana X;Hristova M;Da Costa C;Patodia S;Thei L;Makwana M;Spencer-Dene B;Latouche M;Mirsky R;Jessen KR;Klein R;Raivich G;Behrens A
通讯作者：
Behrens A
影响因子：
3.5
作者：
Groh, Janos;Heinl, Kristina;Martini, Rudolf
通讯作者：
Martini, Rudolf
DOI：
10.1084/jem.20072254
发表时间：
2008-09-29
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Gilchrist M;Henderson WR Jr;Clark AE;Simmons RM;Ye X;Smith KD;Aderem A
通讯作者：
Aderem A
影响因子：
4.8
作者：
Hollis ER 2nd;Zou Y
通讯作者：
Zou Y