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Toward unraveling the complexity of simple epithelial keratins in human disease
M. Bishr Omary, … , Pavel Strnad, Shinichiro Hanada
M. Bishr Omary, … , Pavel Strnad, Shinichiro Hanada
Published July 1, 2009
Citation Information: J Clin Invest. 2009;119(7):1794-1805. https://doi.org/10.1172/JCI37762.
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Review Series

Toward unraveling the complexity of simple epithelial keratins in human disease

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Abstract

Simple epithelial keratins (SEKs) are found primarily in single-layered simple epithelia and include keratin 7 (K7), K8, K18–K20, and K23. Genetically engineered mice that lack SEKs or overexpress mutant SEKs have helped illuminate several keratin functions and served as important disease models. Insight into the contribution of SEKs to human disease has indicated that K8 and K18 are the major constituents of Mallory-Denk bodies, hepatic inclusions associated with several liver diseases, and are essential for inclusion formation. Furthermore, mutations in the genes encoding K8, K18, and K19 predispose individuals to a variety of liver diseases. Hence, as we discuss here, the SEK cytoskeleton is involved in the orchestration of several important cellular functions and contributes to the pathogenesis of human liver disease.

Authors

M. Bishr Omary, Nam-On Ku, Pavel Strnad, Shinichiro Hanada

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Figure 3

Mechanisms and factors involved in MDB formation.

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Mechanisms and factors involved in MDB formation.
(A) Keratin filament r...
(A) Keratin filament reorganization into deposits, granules, or aggregates involves several physiologic (e.g., mitosis and apoptosis) and pathologic (e.g., aggregates that include or exclude K8 and K18 found in the context of several liver disorders) conditions that result in MDB or non-MDB structures. Ub, ubiquitin. (B–E) MDBs (arrows) are identified by pathologists, using H&E staining, as eosinophilic structures (B). Alternatively, MDBs can be visualized by immunofluorescence (C) or by immunohistochemical staining using K8- and K18-specific antibodies (C, green signal, and D), ubiquitin (C, red signal), and p62-specific antibodies (E). The immunological detection methods offer greater sensitivity and specificity than histological MDB staining; however, the latter is currently used clinically and is broadly accepted. Note the similar morphology of MDBs that are identified in mice fed DDC and seen in humans with alcoholic steatohepatitis (ASH).

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