ROS-Induced JNK and p38 Signaling Is Required for Unpaired Cytokine Activation during Drosophila Regeneration.
ROS-Induced JNK and p38 Signaling Is Required for Unpaired Cytokine Activation during Drosophila Regeneration.
复制标题
ROS诱导的JNK和p38信号传导是果蝇再生过程中未配对的细胞因子激活所必需的。
DOI：
10.1371/journal.pgen.1005595
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发表时间：
2015-10
期刊：
影响因子：
4.5
通讯作者：
Serras F
中科院分区：
文献类型：
--
作者：
Santabárbara-Ruiz P;López-Santillán M;Martínez-Rodríguez I;Binagui-Casas A;Pérez L;Milán M;Corominas M;Serras F
在凋亡刺激后，上皮细胞通过激活增殖来补偿死细胞留下的间隙。这导致了死亡细胞向周围的活细胞发出信号以维持体内平衡的建议。虽然这些信号的性质尚不清楚，但活性氧（ROS）可以作为信号传导机制，因为它们可以触发促炎反应以保护上皮细胞免受环境损伤。ROS是否从死亡细胞中产生以及ROS引发的遗传反应是理解果蝇成虫盘再生的关键。我们通过基因诱导翅盘中的细胞死亡，监测ROS的产生并分析修复所需的信号。我们发现，细胞死亡会产生大量的ROS，这些ROS会传播到附近的存活细胞。活化的ROS激活p38并诱导可耐受水平的JNK。JNK和p38的激活导致细胞因子Unpaired（Upd）的表达，其触发再生所需的JAK/STAT信号通路。我们的研究结果表明，ROS/JNK/p38/Upd应激反应模块恢复组织稳态。该模块不仅在细胞死亡诱导后被激活，而且在物理损伤后也被激活，并且揭示了对椎间盘再生的最早反应之一。再生生物学致力于揭示由组织损伤引发的遗传网络。再生可以在细胞死亡或损伤造成的损伤后发生。我们使用果蝇的成虫盘，我们在其中通过基因激活细胞凋亡或物理去除某些部分，并监测修复损伤的能力。我们发现，垂死的细胞产生活性氧簇（ROS）的爆发，激活周围活细胞中的JNK和p38信号通路。这些途径的作用对于未配对的细胞因子（Upd）的激活是必要的。最终，Upd将打开JAK/STAT信号通路，诱导再生生长。因此，我们在这里提出了一个模块的信号，依赖于氧化应激，并通过p38-JNK的相互作用，将激活依赖于精氨酸的再生。
Upon apoptotic stimuli, epithelial cells compensate the gaps left by dead cells by activating proliferation. This has led to the proposal that dying cells signal to surrounding living cells to maintain homeostasis. Although the nature of these signals is not clear, reactive oxygen species (ROS) could act as a signaling mechanism as they can trigger pro-inflammatory responses to protect epithelia from environmental insults. Whether ROS emerge from dead cells and what is the genetic response triggered by ROS is pivotal to understand regeneration of Drosophila imaginal discs. We genetically induced cell death in wing imaginal discs, monitored the production of ROS and analyzed the signals required for repair. We found that cell death generates a burst of ROS that propagate to the nearby surviving cells. Propagated ROS activate p38 and induce tolerable levels of JNK. The activation of JNK and p38 results in the expression of the cytokines Unpaired (Upd), which triggers the JAK/STAT signaling pathway required for regeneration. Our findings demonstrate that this ROS/JNK/p38/Upd stress responsive module restores tissue homeostasis. This module is not only activated after cell death induction but also after physical damage and reveals one of the earliest responses for imaginal disc regeneration. Regenerative biology pursues to unveil the genetic networks triggered by tissue damage. Regeneration can occur after damage by cell death or by injury. We used the imaginal disc of Drosophila in which we genetically activated apoptosis or physically removed some parts and monitored the capacity to repair the damage. We found that dying cells generate a burst of reactive oxygen species (ROS) necessary to activate JNK and p38 signaling pathways in the surrounding living cells. The action of these pathways is necessary for the activation of the cytokines Unpaired (Upd). Eventually, Upd will turn on the JAK/STAT signaling pathway to induce regenerative growth. Thus, we present here a module of signals that depends on oxidative stress and that, through the p38-JNK interplay, will activate cytokine-dependent regeneration.