Adaptive remodeling of the biliary architecture underlies liver homeostasis
Adaptive remodeling of the biliary architecture underlies liver homeostasis
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DOI：
10.1002/hep.27685
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发表时间：
2015-06-01
期刊：
影响因子：
13.5
通讯作者：
Itoh, Tohru
中科院分区：
文献类型：
--
作者：
Kaneko, Kota;Kamimoto, Kenji;Itoh, Tohru
作为新陈代谢和解毒的中心，肝脏天生就容易受到毒素或化学物质造成的各种损害。在人类和动物模型的各种肝脏疾病的组织病理学检查中，经常观察到具有胆管上皮表型的细胞群的诱导，其中包括祖细胞样细胞，被称为肝祖细胞，并与再生有关。然而，这种现象背后的组织动力学在很大程度上仍不清楚。我们已经开发了一种简单的成像技术来揭示小鼠肝脏中扩散的胆道的全局和细微尺度的结构。使用这种新的方法，我们证明了肝祖细胞的出现和扩张实际上反映了小鼠肝损伤模型中肝内胆管树的结构变化。随着慢性损伤的进展，胆管分支的面积逐渐扩大。已知的参与肝祖细胞调控的相关调控信号，包括成纤维细胞生长因子7和肿瘤坏死因子样的弱凋亡诱导物，可以通过不同的方式调节胆管上皮细胞的动力学。重要的是，胆管树的结构变化是多样的，并与实质损伤的类型很好地对应。也就是说，当慢性肝细胞损伤发生在中心周围区域时，胆管分支表现为从门脉周围区域延伸的结构，并明显朝向远端损伤区域。结论：肝胆系统具有独特的、前所未有的结构灵活性，可以根据不同的损伤条件进行动态和适应性的重塑，这种组织可塑性应该是维持肝脏动态平衡的重要组成部分。(《肝病》2015；61：2056-2066)
Serving as the center for metabolism and detoxification, the liver is inherently susceptible to a wide variety of damage imposed by toxins or chemicals. Induction of cell populations with biliary epithelial phenotypes, which include progenitor-like cells and are referred to as liver progenitor cells, is often observed in histopathological examination of various liver diseases in both human patients and animal models and has been implicated in regeneration. However, the tissue dynamics underlying this phenomenon remains largely unclear. We have developed a simple imaging technique to reveal the global and fine-scale architecture of the biliary tract spreading in the mouse liver. Using this novel method, we show that the emergence and expansion of liver progenitor cells actually reflect structural transformation of the intrahepatic biliary tree in mouse liver injury models. The biliary branches expanded their area gradually and contiguously along with the course of chronic injury. Relevant regulatory signals known to be involved in liver progenitor cell regulation, including fibroblast growth factor 7 and tumor necrosis factor-like weak inducer of apoptosis, can modulate the dynamics of the biliary epithelium in different ways. Importantly, the structural transformations of the biliary tree were diverse and corresponded well with the parenchymal injury patterns. That is, when chronic hepatocyte damage was induced in the pericentral area, the biliary branches exhibited an extended structure from the periportal area with apparent tropism toward the distant injured area. Conclusion: The hepatobiliary system possesses a unique and unprecedented structural flexibility and can remodel dynamically and adaptively in response to various injury conditions; this type of tissue plasticity should constitute an essential component to maintain liver homeostasis. (Hepatology 2015;61:2056-2066)