ArticleThe Journal of cell biology1995
Chronic hepatitis, hepatocyte fragility, and increased soluble phosphoglycokeratins in transgenic mice expressing a keratin 18 conserved arginine mutant.
Article in The Journal of cell biology, 1995. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 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.
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Who cites it
66 citing papers in PubMed, 159 citations in OpenAlex.
- Mechanics of cell sheets: plectin as an integrator of cytoskeletal networks.Open biology · 2025Review
- Shifts in keratin isoform expression activate motility signals during wound healing.Developmental cell · 2024Article
- Keratin isoform shifts modulate motility signals during wound healing.bioRxiv : the preprint server for biology · 2024Article
- Deacetylation via SIRT2 prevents keratin-mutation-associated injury and keratin aggregation.JCI insight · 2023Article
- Roles of Keratins in Intestine.International journal of molecular sciences · 2022Review
- Article
- Keratin 8/18 Regulate the Akt Signaling Pathway.International journal of molecular sciences · 2021Article
- Keratin 7 Is a Constituent of the Keratin Network in Mouse Pancreatic Islets and Is Upregulated in Experimental Diabetes.International journal of molecular sciences · 2021Article
- Revealing the Roles of Keratin 8/18-Associated Signaling Proteins Involved in the Development of Hepatocellular Carcinoma.International journal of molecular sciences · 2021Review
- Filaments and phenotypes: cellular roles and orphan effects associated with mutations in cytoplasmic intermediate filament proteins.F1000Research · 2019Review
- The role of keratins in the digestive system: lessons from transgenic mouse models.Histochemistry and cell biology · 2018Review
- Intermediate filament proteins of digestive organs: physiology and pathophysiology.American journal of physiology. Gastrointestinal and liver physiology · 2017Review
- Keratins: Biomarkers and modulators of apoptotic and necrotic cell death in the liver.Hepatology (Baltimore, Md.) · 2016Review
- Review
- High-Throughput Screening for Drugs that Modulate Intermediate Filament Proteins.Methods in enzymology · 2016Article
- PKC412 normalizes mutation-related keratin filament disruption and hepatic injury in mice by promoting keratin-myosin binding.Hepatology (Baltimore, Md.) · 2015Article
- Absence of keratins 8 and 18 in rodent epithelial cell lines associates with keratin gene mutation and DNA methylation: Cell line selective effects on cell invasion.Experimental cell research · 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
- CD73 (ecto-5'-nucleotidase) hepatocyte levels differ across mouse strains and contribute to mallory-denk body formation.Hepatology (Baltimore, Md.) · 2013Article
- Predisposition to apoptosis in keratin 8-null liver is related to inactivation of NF-κB and SAPKs but not decreased c-Flip.Biology open · 2013Article
6 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The two major intermediate filament proteins in glandular epithelia are keratin polypeptides 8 and 18 (K8/18). To evaluate the function and potential disease association of K18, we examined the effects of mutating a highly conserved arginine (arg89) of K18. Expression of K18 arg89-->his/cys and its normal K8 partner in cultured cells resulted in punctate staining as compared with the typical filaments obtained after expression of wild-type K8/18. Generation of transgenic mice expressing human K18 arg89-->cys resulted in marked disruption of liver and pancreas keratin filament networks. The most prominent histologic abnormalities were liver inflammation and necrosis that appeared at a young age in association with hepatocyte fragility and serum transaminase elevation. These effects were caused by the mutation since transgenic mice expressing wild-type human K18 showed a normal phenotype. A relative increase in the phosphorylation and glycosylation of detergent solubilized K8/18 was also noted in vitro and in transgenic animals that express mutant K18. Our results indicate that the highly conserved arg plays an important role in glandular keratin organization and tissue fragility as already described for epidermal keratins. Phosphorylation and glycosylation alterations in the arg mutant keratins may account for some of the potential changes in the cellular function of these proteins. Mice expressing mutant K18 provide a novel animal model for human chronic hepatitis, and for studying the tissue specific function(s) of K8/18.
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Registered trials
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