Segregated Hepatocyte Proliferation and Metabolic States Within the Regenerating Mouse Liver
Segregated Hepatocyte Proliferation and Metabolic States Within the Regenerating Mouse Liver
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DOI：
10.1002/hep4.1102
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发表时间：
2017-11-01
影响因子：
5.1
通讯作者：
Herr, Winship
中科院分区：
文献类型：
--
作者：
Minocha, Shilpi;Villeneuve, Dominic;Herr, Winship
哺乳动物部分肝切除术（PH）诱导剩余组织的协调代偿性增生或再生，以恢复肝脏质量;在此过程中，维持肝脏功能。我们在喂食和光/暗夹带的动物进行假手术或PH手术的小鼠中探索了这一过程。早期（即，10小时），无论是假手术还是PH手术，肝细胞与门静脉和中央静脉等距（即，小叶中）积累G1期细胞分裂周期标记物细胞周期蛋白D1。然而，到24小时，细胞周期蛋白D1消失不PH，但在中叶肝细胞PH后得到加强。在PH后48小时和禁食2小时，同步有丝分裂的肝细胞具有较少的糖原比周围的非增殖肝细胞。不同的糖原含量产生了一个明显的纠缠模式的增殖小叶和非增殖门静脉周围和中央周围的肝细胞。非增殖的肝细胞保持正常的肝脏特性。结论：在PH后再生的小鼠肝脏中，二元开关将小叶中细胞分离为与维持代谢功能的非增殖门静脉周围细胞和中央周围细胞并排增殖。我们的研究结果还表明，肝再生的机制显示进化的灵活性。
Mammalian partial hepatectomy (PH) induces an orchestrated compensatory hyperplasia, or regeneration, in remaining tissue to restore liver mass; during this process, liver functions are maintained. We probed this process in mice with feeding-and light/dark-entrained animals subjected to sham or PH surgery. Early on (i.e., 10 hours), irrespective of sham or PH surgery, hepatocytes equidistant from the portal and central veins (i.e., midlobular) accumulated the G1-phase cell-division-cycle marker cyclin D1. By 24 hours, however, cyclin D1 disappeared absent PH but was reinforced in midlobular hepatocytes after PH. At 48 hours after PH and 2 hours fasting, synchronously mitotic hepatocytes possessed less glycogen than surrounding nonproliferating hepatocytes. The differential glycogen content generated a conspicuous entangled pattern of proliferating midlobular and nonproliferating periportal and pericentral hepatocytes. The nonproliferating hepatocytes maintained aspects of normal liver properties. Conclusion: In the post-PH regenerating mouse liver, a binary switch segregates midlobular cells to proliferate side-by-side with nonproliferating periportal and pericentral cells, which maintain metabolic functions. Our results also indicate that mechanisms of liver regeneration display evolutionary flexibility.