| http://purl.uniprot.org/citations/10821760 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/10821760 | http://www.w3.org/2000/01/rdf-schema#comment | "Pancreatic acini and islets are believed to differentiate from common ductal precursors through a process requiring various growth factors. Epidermal growth factor receptor (EGF-R) is expressed throughout the developing pancreas. We have analyzed here the pancreatic phenotype of EGF-R deficient (-/-) mice, which generally die from epithelial immaturity within the first postnatal week. The pancreata appeared macroscopically normal. The most striking feature of the EGF-R (-/-) islets was that instead of forming circular clusters, the islet cells were mainly located in streak-like structures directly associated with pancreatic ducts. Based on BrdU-labelling, proliferation of the neonatal EGF-R (-/-) beta-cells was significantly reduced (2.6+/-0.4 versus 5.8+/-0.9%, P<0.01) and the difference persisted even at 7-11 days of age. Analysis of embryonic pancreata revealed impaired branching morphogenesis and delayed islet cell differentiation in the EGF-R (-/-) mice. Islet development was analyzed further in organ cultures of E12.5 pancreata. The proportion of insulin-positive cells was significantly lower in the EGF-R (-/-) explants (27+/-6 versus 48+/-8%, P<0.01), indicating delayed differentiation of the beta cells. Branching of the epithelium into ducts was also impaired. Matrix metalloproteinase (MMP-2 and MMP-9) activity was reduced 20% in EGF-R (-/-) late-gestation pancreata, as measured by gelatinase assays. Furthermore, the levels of secreted plasminogen activator inhibitor-1 (PAI-1) were markedly higher, while no apparent differences were seen in the levels of active uPA and tPa between EGF-R (-/-) and wild-type pancreata. Our findings suggest that the perturbation of EGF-R-mediated signalling can lead to a generalized proliferation defect of the pancreatic epithelia associated with a delay in beta cell development and disturbed migration of the developing islet cells as they differentiate from their precursors. Upregulated PAI-1 production and decreased gelatinolytic activity correlated to this migration defect. An intact EGF-R pathway appears to be a prerequisite for normal pancreatic development."xsd:string |
| http://purl.uniprot.org/citations/10821760 | http://purl.org/dc/terms/identifier | "doi:10.1242/dev.127.12.2617"xsd:string |
| http://purl.uniprot.org/citations/10821760 | http://purl.uniprot.org/core/author | "Otonkoski T."xsd:string |
| http://purl.uniprot.org/citations/10821760 | http://purl.uniprot.org/core/author | "Ustinov J."xsd:string |
| http://purl.uniprot.org/citations/10821760 | http://purl.uniprot.org/core/author | "Miettinen P.J."xsd:string |
| http://purl.uniprot.org/citations/10821760 | http://purl.uniprot.org/core/author | "Lehtonen E."xsd:string |
| http://purl.uniprot.org/citations/10821760 | http://purl.uniprot.org/core/author | "Huotari M."xsd:string |
| http://purl.uniprot.org/citations/10821760 | http://purl.uniprot.org/core/author | "Keski-Oja J."xsd:string |
| http://purl.uniprot.org/citations/10821760 | http://purl.uniprot.org/core/author | "Palgi J."xsd:string |
| http://purl.uniprot.org/citations/10821760 | http://purl.uniprot.org/core/author | "Koivisto T."xsd:string |
| http://purl.uniprot.org/citations/10821760 | http://purl.uniprot.org/core/author | "Rasilainen S."xsd:string |
| http://purl.uniprot.org/citations/10821760 | http://purl.uniprot.org/core/date | "2000"xsd:gYear |
| http://purl.uniprot.org/citations/10821760 | http://purl.uniprot.org/core/name | "Development"xsd:string |
| http://purl.uniprot.org/citations/10821760 | http://purl.uniprot.org/core/pages | "2617-2627"xsd:string |
| http://purl.uniprot.org/citations/10821760 | http://purl.uniprot.org/core/title | "Impaired migration and delayed differentiation of pancreatic islet cells in mice lacking EGF-receptors."xsd:string |
| http://purl.uniprot.org/citations/10821760 | http://purl.uniprot.org/core/volume | "127"xsd:string |
| http://purl.uniprot.org/citations/10821760 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/10821760 |
| http://purl.uniprot.org/citations/10821760 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/10821760 |
| http://purl.uniprot.org/uniprot/#_A2AS86-mappedCitation-10821760 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/10821760 |
| http://purl.uniprot.org/uniprot/#_A0A0R4IZW5-mappedCitation-10821760 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/10821760 |
| http://purl.uniprot.org/uniprot/#_A2A5K8-mappedCitation-10821760 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/10821760 |
| http://purl.uniprot.org/uniprot/#_A0A1B0GS88-mappedCitation-10821760 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/10821760 |
| http://purl.uniprot.org/uniprot/#_B2KGF7-mappedCitation-10821760 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/10821760 |
| http://purl.uniprot.org/uniprot/#_P70424-mappedCitation-10821760 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/10821760 |