Animal models of biliary injury and altered bile acid metabolism.
Animal models of biliary injury and altered bile acid metabolism.
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DOI：
10.1016/j.bbadis.2017.06.027
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发表时间：
2018-04
期刊：
影响因子：
--
通讯作者：
Calvisi DF
中科院分区：
文献类型：
--
作者：
Mariotti V;Strazzabosco M;Fabris L;Calvisi DF
在过去的25年中，已经产生了许多动物模型，主要是啮齿动物，目的是模拟胆汁淤积性肝损伤，从而提供体内工具来研究胆道修复的机制，并最终测试创新治疗的疗效。尽管应用于这些模型的基本限制，例如与人类相比，啮齿动物中不同的免疫系统和调节肝脏稳态的不同代谢，但多种方法，例如手术，（胆管结扎），化学诱导（3，5-二乙氧羰基-1，4-二氢可力丁，DDC，α-萘异硫氰酸酯，ANIT），病毒感染（恒河猴轮状病毒A型，RRV-A）和遗传操作（Mdr 2，Cftr，Pkd 1，Pkd 2，Prkcsh，Sec 63，Pkhd 1）已经被开发。总体而言，它们导致了一系列肝脏表型，概括了胆道损伤和胆汁酸代谢改变的主要特征，如胆管反应、胆管周围炎症和纤维化、阻塞性胆汁淤积和胆道发育不全。虽然对人类环境的可重复性有限，但这些小鼠模型为我们提供了随时间推移探索促进胆汁淤积性疾病进展的基本机制的能力。此外，最近对基因工程小鼠的研究揭示了使胆管细胞成为肝脏修复关键参与者的“核心”途径。在这篇综述中，我们将突出主要的表型特征，更有趣的特点和这些小鼠模型的不同缺点。
In the last 25 years, a number of animal models, mainly rodents, have been generated with the goal to mimic cholestatic liver injuries and, thus, to provide in vivo tools to investigate the mechanisms of biliary repair and, eventually, to test the efficacy of innovative treatments. Despite fundamental limitations applying to these models, such as the distinct immune system and the different metabolism regulating liver homeostasis in rodents when compared to humans, multiple approaches, such as surgery (bile duct ligation), chemical-induced (3,5-diethoxycarbonyl-1,4-dihydrocollidine, DDC, α-naphthylisothiocyanate, ANIT), viral infections (Rhesus rotavirustype A, RRV-A), and genetic manipulation (Mdr2, Cftr, Pkd1, Pkd2, Prkcsh, Sec63, Pkhd1) have been developed. Overall, they have led to a range of liver phenotypes recapitulating the main features of biliary injury and altered bile acid metabolisms, such as ductular reaction, peribiliary inflammation and fibrosis, obstructive cholestasis and biliary dysgenesis. Although with a limited translability to the human setting, these mouse models have provided us with the ability to probe over time the fundamental mechanisms promoting cholestatic disease progression. Moreover, recent studies from genetically engineered mice have unveiled ‘core’ pathways that make the cholangiocyte a pivotal player in liver repair. In this review, we will highlight the main phenotypic features, the more interesting peculiarities and the different drawbacks of these mouse models.
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影响因子：
3.8
作者：
CONNOLLY, AK;PRICE, SC;HINTON, RH
通讯作者：
HINTON, RH
BIP介导的分子机制的内质网的Sec61易位门控。
DOI：
10.1083/jcb.200409174
发表时间：
2005-01-31
期刊：
The Journal of cell biology
影响因子：
--
作者：
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通讯作者：
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影响因子：
1.5
作者：
Calvisi, DF;Thorgeirsson, SS
通讯作者：
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影响因子：
30.8
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影响因子：
30.8
作者：
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通讯作者：
Jansen, JBMJ