Akt/mTOR integrate energy metabolism with Wnt signal to influence wound epithelium growth in Gekko Japonicus.
Akt/mTOR integrate energy metabolism with Wnt signal to influence wound epithelium growth in Gekko Japonicus.
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DOI：
10.1038/s42003-022-04004-5
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发表时间：
2022-09-27
影响因子：
5.9
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中科院分区：
文献类型：
--
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创伤上皮的形成启动了壁虎断尾的再生。能量代谢是生物生长不可缺少的过程，通常受温度的影响。本研究揭示了低温降低了无蹼壁虎断尾的能量代谢水平，抑制了断尾的再生。我们进一步发现低温减弱了再生组织中蛋白激酶B（Akt）和哺乳动物雷帕霉素靶蛋白（mTOR）在损伤信号下的活化，并且Akt的抑制阻碍了伤口上皮的增殖。此外，无翅/整合（Wnt）抑制通过抑制Akt活化来抑制上皮细胞增殖和形成。最后，低温升高腺苷酸激活激酶（AMPK）通路的活性，进而减弱伤口上皮的形成。同时，mTOR下调或AMPK上调与更差的伤口上皮形成相关。总之，低温通过影响包括Akt/mTOR和AMPK信号传导在内的能量感觉通路来限制伤口上皮的形成，这也受到损伤诱导的Wnt信号的调节。我们的研究结果提供了一个机制，将损伤信号与代谢途径，以促进再生。低温通过影响能量感受性Akt/mTOR通路抑制壁虎断尾再生，该通路也受到损伤诱导的Wnt信号的调节。
The formation of wound epithelium initiates regeneration of amputated tail in Gekko japonicus. Energy metabolism is indispensable for the growth of living creatures and typically influenced by temperature. In this study, we reveal that low temperature lowers energy metabolism level and inhibits the regeneration of amputated tails of Gekko japonicus. We further find that low temperature attenuates the activation of protein kinase B (Akt) and mammalian target of rapamycin (mTOR) in regenerated tissues upon injury signals, and the inhibition of Akt hinders proliferation of the wound epithelium. Additionally, wingless/integrated (Wnt) inhibition suppresses epithelium proliferation and formation by inhibiting Akt activation. Finally, low temperature elevates the activity of adenylate-activated kinase (AMPK) pathway and in turn attenuates wound epithelium formation. Meanwhile, either mTOR downregulation or AMPK upregulation is associated with worse wound epithelium formation. Summarily, low temperature restricts wound epithelium formation by influencing energy sensory pathways including Akt/mTOR and AMPK signaling, which is also modulated by injury induced Wnt signal. Our results provide a mechanism that incorporates the injury signals with metabolic pathway to facilitate regeneration. Low temperature inhibits the regeneration of amputated tails of Gekko japonicus by influencing the energy sensory Akt/mTOR pathway, which is also modulated by injury-induced Wnt signal.
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Sartorelli, Vittorio
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