Vagus-macrophage-hepatocyte link promotes post-injury liver regeneration and whole-body survival through hepatic FoxM1 activation
Vagus-macrophage-hepatocyte link promotes post-injury liver regeneration and whole-body survival through hepatic FoxM1 activation
复制标题
DOI：
10.1038/s41467-018-07747-0
复制
发表时间：
2018-12-13
影响因子：
16.6
通讯作者：
Katagiri, Hideki
中科院分区：
文献类型：
--
作者：
Izumi, Tomohito;Imai, Junta;Katagiri, Hideki
肝脏具有很高的再生能力。肝再生是一种代偿性反应，它克服了器官缺陷引起的全身内环境平衡紊乱。在这里，我们表明，迷走神经-巨噬细胞-肝细胞连接调节肝损伤后的急性肝再生，这一系统是促进生存的关键。部分肝切除术（PHx）后肝脏Foxm 1迅速上调。肝分支迷走神经切断术（HV）抑制这种上调和肝细胞增殖，从而增加死亡率。此外，在迷走神经切断的小鼠中，肝脏FoxM 1补充逆转了肝脏再生的抑制，并阻断了PHx后死亡率的增加。肝脏巨噬细胞耗竭抑制PHx后Foxm 1上调和残肝再生，并增加死亡率。肝IL-6迅速上升后PHx，这是抑制HV，毒蕈碱阻断或常驻巨噬细胞耗竭。此外，IL-6中和抑制PHx后Foxm 1上调和残肝再生。总的来说，迷走神经信号介导的肝巨噬细胞中IL-6的产生上调肝细胞FoxM 1，导致肝再生并确保存活。
The liver possesses a high regenerative capacity. Liver regeneration is a compensatory response overcoming disturbances of whole-body homeostasis provoked by organ defects. Here we show that a vagus-macrophage-hepatocyte link regulates acute liver regeneration after liver injury and that this system is critical for promoting survival. Hepatic Foxm1 is rapidly upregulated after partial hepatectomy (PHx). Hepatic branch vagotomy (HV) suppresses this upregulation and hepatocyte proliferation, thereby increasing mortality. In addition, hepatic FoxM1 supplementation in vagotomized mice reverses the suppression of liver regeneration and blocks the increase in post-PHx mortality. Hepatic macrophage depletion suppresses both post-PHx Foxm1 upregulation and remnant liver regeneration, and increases mortality. Hepatic Il-6 rises rapidly after PHx and this is suppressed by HV, muscarinic blockade or resident macrophage depletion. Furthermore, IL-6 neutralization suppresses post-PHx Foxm1 upregulation and remnant liver regeneration. Collectively, vagal signal-mediated IL-6 production in hepatic macrophages upregulates hepatocyte FoxM1, leading to liver regeneration and assures survival.