Zatloukal Kurt, French Samuel W, Stumptner Cornelia, Strnad Pavel, Harada Masaru, Toivola Diana M, Cadrin Monique, Omary M Bishr
Institute of Pathology, Medical University of Graz, Auenbruggerplatz 25, A-8036 Graz, Austria.
Exp Cell Res. 2007 Jun 10;313(10):2033-49. doi: 10.1016/j.yexcr.2007.04.024. Epub 2007 Apr 27.
Frank B. Mallory described cytoplasmic hyaline inclusions in hepatocytes of patients with alcoholic hepatitis in 1911. These inclusions became known as Mallory bodies (MBs) and have since been associated with a variety of other liver diseases including non-alcoholic fatty liver disease. Helmut Denk and colleagues described the first animal model of MBs in 1975 that involves feeding mice griseofulvin. Since then, mouse models have been instrumental in helping understand the pathogenesis of MBs. Given the tremendous contributions made by Denk to the field, we propose renaming MBs as Mallory-Denk bodies (MDBs). The major constituents of MDBs include keratins 8 and 18 (K8/18), ubiquitin, and p62. The relevant proteins and cellular processes that contribute to MDB formation and accumulation include the type of chronic stress, the extent of stress-induced protein misfolding and consequent proteasome overload, a K8-greater-than-K18 ratio, transamidation of K8 and other proteins, presence of p62 and autophagy. Although it remains unclear whether MDBs serve a bystander, protective or injury promoting function, they do serve an important role as histological and potential progression markers in several liver diseases.
1911年，弗兰克·B·马洛里描述了酒精性肝炎患者肝细胞中的细胞质透明包涵体。这些包涵体后来被称为马洛里小体（MBs），此后还与包括非酒精性脂肪性肝病在内的多种其他肝脏疾病相关联。1975年，赫尔穆特·登克及其同事描述了首个MBs动物模型，该模型涉及给小鼠喂食灰黄霉素。从那时起，小鼠模型在帮助理解MBs的发病机制方面发挥了重要作用。鉴于登克对该领域做出的巨大贡献，我们提议将MBs重新命名为马洛里-登克小体（MDBs）。MDBs的主要成分包括角蛋白8和18（K8/18）、泛素和p62。导致MDB形成和积累的相关蛋白质和细胞过程包括慢性应激的类型、应激诱导的蛋白质错误折叠程度以及随之而来的蛋白酶体过载、K8与K18的比例、K8和其他蛋白质的转酰胺作用、p62的存在以及自噬。尽管尚不清楚MDBs是发挥旁观者、保护还是促进损伤的功能，但它们在几种肝脏疾病中作为组织学和潜在进展标志物确实发挥着重要作用。
