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dc.contributor.authorCasanova, M. Llanos-
dc.contributor.authorMorreale de Escobar, Gabriella-
dc.contributor.authorJorcano, José L.-
dc.date.accessioned2010-05-17T12:19:31Z-
dc.date.available2010-05-17T12:19:31Z-
dc.date.issued1999-06-
dc.identifier.citationJournal of Clinical Investigation 103(11): 1587-1595 (1999)en_US
dc.identifier.issn0021-9738-
dc.identifier.urihttp://hdl.handle.net/10261/24391-
dc.description9 pages, 6 figures, 2 tables.-- et al.en_US
dc.description.abstractKeratins K8 and K18 are the major components of the intermediate-filament cytoskeleton of simple epithelia. Increased levels of these keratins have been correlated with various tumor cell characteristics, including progression to malignancy, invasive behavior, and drug sensitivity, although a role for K8/K18 in tumorigenesis has not yet been demonstrated. To examine the function of these keratins, we generated mice expressing the human K8 (hk8) gene, which leads to a moderate keratin-content increase in their simple epithelia. These mice displayed progressive exocrine pancreas alterations, including dysplasia and loss of acinar architecture, redifferentiation of acinar to ductal cells, inflammation, fibrosis, and substitution of exocrine by adipose tissue, as well as increased cell proliferation and apoptosis. Histological changes were not observed in other simple epithelia, such as the liver. Electron microscopy showed that transgenic acinar cells have keratins organized in abundant filament bundles dispersed throughout the cytoplasm, in contrast to control acinar cells, which have scarce and apically concentrated filaments. The phenotype found was very similar to that reported for transgenic mice expressing a dominant-negative mutant TGF-β type II receptor (TGFβRII mice). We show that these TGFβRII mutant mice also have elevated K8/K18 levels. These results indicate that simple epithelial keratins play a relevant role in the regulation of exocrine pancreas homeostasis and support the idea that disruption of mechanisms that normally regulate keratin expression in vivo could be related to inflammatory and neoplastic pancreatic disorders.en_US
dc.description.sponsorshipThis work was supported in part by grant PB 94-1230 of the Spanish Dirección General de Investigación Científica y Tecnológica.en_US
dc.format.extent395254 bytes-
dc.format.mimetypeapplication/pdf-
dc.language.isoengen_US
dc.publisherAmerican Society for Clinical Investigationen_US
dc.rightsopenAccessen_US
dc.titleExocrine pancreatic disorders in transsgenic mice expressing human keratin 8en_US
dc.typeartículoen_US
dc.identifier.doi10.1172/JCI5343-
dc.description.peerreviewedPeer revieweden_US
dc.relation.publisherversionhttp://dx.doi.org/10.1172/JCI5343en_US
dc.identifier.pmid10359568-
dc.type.coarhttp://purl.org/coar/resource_type/c_6501es_ES
item.openairetypeartículo-
item.grantfulltextopen-
item.cerifentitytypePublications-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.fulltextWith Fulltext-
item.languageiso639-1en-
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