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再生小鼠肝脏内肝细胞增殖和代谢状态的分离

Segregated hepatocyte proliferation and metabolic states within the regenerating mouse liver.

作者信息

Minocha Shilpi, Villeneuve Dominic, Rib Leonor, Moret Catherine, Guex Nicolas, Herr Winship

机构信息

Center for Integrative Genomics, Génopode University of Lausanne Lausanne Switzerland.

Vital-IT Group, SIB Swiss Institute of Bioinformatics, Génopode Lausanne Switzerland.

出版信息

Hepatol Commun. 2017 Sep 26;1(9):871-885. doi: 10.1002/hep4.1102. eCollection 2017 Nov.

DOI:10.1002/hep4.1102
PMID:29404499
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5721458/
Abstract

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. : 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. ( 2017;1:871-885).

摘要

哺乳动物部分肝切除术(PH)可诱导剩余组织中精心编排的代偿性增生或再生,以恢复肝脏质量;在此过程中,肝脏功能得以维持。我们在喂食及受光/暗周期调节的小鼠中探究了这一过程,这些小鼠接受了假手术或PH手术。早期(即10小时),无论进行假手术还是PH手术,距门静脉和中央静脉等距的肝细胞(即小叶中部)都会积累G1期细胞分裂周期标记物细胞周期蛋白D1。然而,到24小时时,若未进行PH手术,细胞周期蛋白D1会消失,但在PH手术后,小叶中部肝细胞中的该蛋白会增强。在PH手术后48小时及禁食2小时时,同步有丝分裂的肝细胞所含糖原比周围未增殖的肝细胞少。糖原含量的差异在增殖的小叶中部肝细胞与未增殖的门静脉周围及中央周围肝细胞之间形成了明显的纠缠模式。未增殖的肝细胞维持着正常肝脏特性的某些方面。:在PH术后再生的小鼠肝脏中,一种二元开关将小叶中部细胞分离出来,使其与维持代谢功能的未增殖的门静脉周围及中央周围细胞并列增殖。我们的结果还表明,肝脏再生机制具有进化灵活性。(2017;1:871 - 885)

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d8f/5721458/5449ec2b3032/HEP4-1-871-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d8f/5721458/9266aff3b931/HEP4-1-871-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d8f/5721458/b4f4f9a2f16d/HEP4-1-871-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d8f/5721458/c982d67cadb5/HEP4-1-871-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d8f/5721458/fa6d90e6149f/HEP4-1-871-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d8f/5721458/cadd8d3ad35e/HEP4-1-871-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d8f/5721458/ad858174ab45/HEP4-1-871-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d8f/5721458/46a632bd7ed5/HEP4-1-871-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d8f/5721458/5449ec2b3032/HEP4-1-871-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d8f/5721458/9266aff3b931/HEP4-1-871-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d8f/5721458/b4f4f9a2f16d/HEP4-1-871-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d8f/5721458/c982d67cadb5/HEP4-1-871-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d8f/5721458/fa6d90e6149f/HEP4-1-871-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d8f/5721458/cadd8d3ad35e/HEP4-1-871-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d8f/5721458/ad858174ab45/HEP4-1-871-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d8f/5721458/46a632bd7ed5/HEP4-1-871-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d8f/5721458/5449ec2b3032/HEP4-1-871-g008.jpg

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