Broad spectrum of hepatocyte inclusions in humans, animals, and experimental models.
Broad spectrum of hepatocyte inclusions in humans, animals, and experimental models.
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人类、动物和实验模型中广泛的肝细胞内含物
DOI：
10.1002/cphy.c120032
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发表时间：
2013
影响因子：
5.8
通讯作者：
Haybaeck J
中科院分区：
文献类型：
--
作者：
Strnad P;Nuraldeen R;Guldiken N;Hartmann D;Mahajan V;Denk H;Haybaeck J
我们专注于肝包涵体，它被定义为细胞内聚集的促炎物质。它们代表了各自人类疾病的既定标志，但与神经退行性疾病中发现的聚集体不同，它们往往没有得到很好的研究。肝包涵体可细分为原发性肝聚集体和在多种组织中发现的聚集体。前者包括在内质网储存疾病中发现的包涵体，如α 1-抗胰蛋白酶聚集体或毛玻璃肝细胞、含p62的包涵体（马洛里-Denk小体和细胞内透明小体）和含卟啉的包涵体。含有p62的聚集体不限于肝脏，但在多种其他疾病中发现，如帕金森病或阿尔茨海默病。包涵体如苍白小体或细胞内透明小体是恶性疾病的典型特征，而其他包涵体（毛玻璃样肝细胞和α1-抗胰蛋白酶聚集体）主要见于非肿瘤组织。不限于肝脏的包涵体通常是由于全身性病毒感染，但也由于糖原代谢破坏或全身性包涵体形成疾病，如多聚谷氨酰胺疾病或结节病。尽管它们具有异质性，但包含物具有几种致病原理，例如一侧的蛋白质损伤/错误折叠与另一侧的修复/降解之间的不平衡。这就是为什么肝聚集体代表了一种有价值的工具，用于研究一般的聚集过程，并提高我们对多种人类疾病中发现的包涵体的理解。© 2013美国生理学会。Compr Physiol 3：1393 - 1436，2013。
We focus on hepatic inclusions, which are defined as intracellular aggregates of stainable substances. They represent established hallmarks of their respective human disorders, but unlike aggregates found in neurodegenerative disorders are often not well studied. Hepatic inclusions can be subdivided into primary liver aggregates and aggregates found in multiple tissues. The former ones consist of inclusions found in endoplasmic reticulum storage diseases such as α 1‐antitrypsin aggregates or ground‐glass hepatocytes, p62‐containing (Mallory‐Denk bodies and intracellular hyaline bodies) and porphyrin‐containing inclusions. p62‐containing aggregates are not restricted to the liver but are found in multiple other disorders such as Parkinson or Alzheimer disease. Inclusions such as pale bodies or intracellular hyaline bodies are typical for malignant disorders while others (ground‐glass hepatocytes and α1‐antitrypsin aggregates) are predominantly seen in non‐neoplastic tissues. The inclusions, which are not restricted to the liver, are often due to a systemic viral infection, but also due to disruption of glycogen metabolism or systemic inclusion‐forming diseases such as polyglutamine disorders or sarcoidosis. Despite their heterogeneity, inclusions share several pathogenic principles such as an imbalance between protein damage/misfolding on one side and repair/degradation on the other side. This is why hepatic aggregates represent a valuable tool to study the aggregation process in general and to improve our understanding of inclusions found in multiple human disorders. © 2013 American Physiological Society.Compr Physiol3:1393‐1436, 2013.
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