ArticleThe Journal of clinical investigation1996
Susceptibility to hepatotoxicity in transgenic mice that express a dominant-negative human keratin 18 mutant.
Article in The Journal of clinical investigation, 1996. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
44 citing papers in PubMed, 122 citations in OpenAlex.
- Mechanics of cell sheets: plectin as an integrator of cytoskeletal networks.Open biology · 2025Review
- Deacetylation via SIRT2 prevents keratin-mutation-associated injury and keratin aggregation.JCI insight · 2023Article
- Keratin 18 is an integral part of the intermediate filament network in murine skeletal muscle.American journal of physiology. Cell physiology · 2020Article
- The role of keratins in the digestive system: lessons from transgenic mouse models.Histochemistry and cell biology · 2018Review
- Site-specific glycosylation regulates the form and function of the intermediate filament cytoskeleton.eLife · 2018Article
- Intermediate Filaments at the Junction of Mechanotransduction, Migration, and Development.Frontiers in cell and developmental biology · 2017Review
- Genetic study of congenital bile-duct dilatation identifies de novo and inherited variants in functionally related genes.BMC medical genomics · 2016Article
- Functional Implications of O-GlcNAcylation-dependent Phosphorylation at a Proximal Site on Keratin 18.The Journal of biological chemistry · 2016Article
- PKC412 normalizes mutation-related keratin filament disruption and hepatic injury in mice by promoting keratin-myosin binding.Hepatology (Baltimore, Md.) · 2015Article
- Prevalence of genetic variants of keratins 8 and 18 in patients with drug-induced liver injury.BMC medicine · 2015Article
- Mutation of caspase-digestion sites in keratin 18 interferes with filament reorganization, and predisposes to hepatocyte necrosis and loss of membrane integrity.Journal of cell science · 2014Article
- Post-translational modifications of intermediate filament proteins: mechanisms and functions.Nature reviews. Molecular cell biology · 2014Review
- Keratin 8 variants are associated with cryptogenic hepatitis.Virchows Archiv : an international journal of pathology · 2012Article
- Cytoskeleton in motion: the dynamics of keratin intermediate filaments in epithelia.The Journal of cell biology · 2011Review
- Absence of keratin 8 confers a paradoxical microflora-dependent resistance to apoptosis in the colon.Proceedings of the National Academy of Sciences of the United States of America · 2011Article
- "Panta rhei": Perpetual cycling of the keratin cytoskeleton.Bioarchitecture · 2011Article
- Keratin variants predispose to acute liver failure and adverse outcome: race and ethnic associations.Gastroenterology · 2010Article
- The role of the ubiquitin proteasome pathway in keratin intermediate filament protein degradation.Proceedings of the American Thoracic Society · 2010Review
- Toward unraveling the complexity of simple epithelial keratins in human disease.The Journal of clinical investigation · 2009Review
- Ubiquitin-proteasome-mediated degradation of keratin intermediate filaments in mechanically stimulated A549 cells.The Journal of biological chemistry · 2008Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Keratins 8 and 18 (K8/18) are intermediate filament phosphoglycoproteins that are expressed preferentially in simple-type epithelia. We recently described transgenic mice that express point-mutant human K18 (Ku, N.-O., S. Michie, R.G. Oshima, and M.B. Omary. 1995. J. Cell Biol. 131:1303-1314) and develop chronic hepatitis and hepatocyte fragility in association with hepatocyte keratin filament disruption. Here we show that mutant K18 expressing transgenic mice are highly susceptible to hepatotoxicity after acute administration of acetaminophen (400 mg/Kg) or chronic ingestion of griseofulvin (1.25% wt/wt of diet). The predisposition to hepatotoxicity results directly from the keratin mutation since nontransgenic or transgenic mice that express normal human K18 are more resistant. Hepatotoxicity was manifested by a significant difference in lethality, liver histopathology, and biochemical serum testing. Keratin glycosylation decreased in all griseofulvin-fed mice, whereas keratin phosphorylation increased dramatically preferentially in mice expressing normal K18. The phosphorylation increase in normal K18 after griseofulvin feeding appears to involve sites that are different to those that increase after partial hepatectomy. Our results indicate that hepatocyte intermediate filament disruption renders mice highly susceptible to hepatotoxicity, and raises the possibility that K18 mutations may predispose to drug hepatotoxicity. The dramatic phosphorylation increase in nonmutant keratins could provide survival advantage to hepatocytes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.