| http://purl.uniprot.org/citations/16236725 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/16236725 | http://www.w3.org/2000/01/rdf-schema#comment | "The core fucosylation (alpha1,6-fucosylation) of glycoproteins is widely distributed in mammalian tissues, and is altered under pathological conditions. To investigate physiological functions of the core fucose, we generated alpha1,6-fucosyltransferase (Fut8)-null mice and found that disruption of Fut8 induces severe growth retardation and death during postnatal development. Histopathological analysis revealed that Fut8(-/-) mice showed emphysema-like changes in the lung, verified by a physiological compliance analysis. Biochemical studies indicated that lungs from Fut8(-/-) mice exhibit a marked overexpression of matrix metalloproteinases (MMPs), such as MMP-12 and MMP-13, highly associated with lung-destructive phenotypes, and a down-regulation of extracellular matrix (ECM) proteins such as elastin, as well as retarded alveolar epithelia cell differentiation. These changes should be consistent with a deficiency in TGF-beta1 signaling, a pleiotropic factor that controls ECM homeostasis by down-regulating MMP expression and inducing ECM protein components. In fact, Fut8(-/-) mice have a marked dysregulation of TGF-beta1 receptor activation and signaling, as assessed by TGF-beta1 binding assays and Smad2 phosphorylation analysis. We also show that these TGF-beta1 receptor defects found in Fut8(-/-) cells can be rescued by reintroducing Fut8 into Fut8(-/-) cells. Furthermore, exogenous TGF-beta1 potentially rescued emphysema-like phenotype and concomitantly reduced MMP expression in Fut8(-/-) lung. We propose that the lack of core fucosylation of TGF-beta1 receptors is crucial for a developmental and progressive/destructive emphysema, suggesting that perturbation of this function could underlie certain cases of human emphysema."xsd:string |
| http://purl.uniprot.org/citations/16236725 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.0507375102"xsd:string |
| http://purl.uniprot.org/citations/16236725 | http://purl.uniprot.org/core/author | "Gu J."xsd:string |
| http://purl.uniprot.org/citations/16236725 | http://purl.uniprot.org/core/author | "Li W."xsd:string |
| http://purl.uniprot.org/citations/16236725 | http://purl.uniprot.org/core/author | "Inoue S."xsd:string |
| http://purl.uniprot.org/citations/16236725 | http://purl.uniprot.org/core/author | "Lopez-Otin C."xsd:string |
| http://purl.uniprot.org/citations/16236725 | http://purl.uniprot.org/core/author | "Nakano M."xsd:string |
| http://purl.uniprot.org/citations/16236725 | http://purl.uniprot.org/core/author | "Lee S.H."xsd:string |
| http://purl.uniprot.org/citations/16236725 | http://purl.uniprot.org/core/author | "Suzuki K."xsd:string |
| http://purl.uniprot.org/citations/16236725 | http://purl.uniprot.org/core/author | "Takahashi M."xsd:string |
| http://purl.uniprot.org/citations/16236725 | http://purl.uniprot.org/core/author | "Wang X."xsd:string |
| http://purl.uniprot.org/citations/16236725 | http://purl.uniprot.org/core/author | "Ikeda Y."xsd:string |
| http://purl.uniprot.org/citations/16236725 | http://purl.uniprot.org/core/author | "Yamaguchi Y."xsd:string |
| http://purl.uniprot.org/citations/16236725 | http://purl.uniprot.org/core/author | "Okabe M."xsd:string |
| http://purl.uniprot.org/citations/16236725 | http://purl.uniprot.org/core/author | "Noda K."xsd:string |
| http://purl.uniprot.org/citations/16236725 | http://purl.uniprot.org/core/author | "Taniguchi N."xsd:string |
| http://purl.uniprot.org/citations/16236725 | http://purl.uniprot.org/core/author | "Uozumi N."xsd:string |
| http://purl.uniprot.org/citations/16236725 | http://purl.uniprot.org/core/author | "Kondo A."xsd:string |
| http://purl.uniprot.org/citations/16236725 | http://purl.uniprot.org/core/author | "Kuwaki T."xsd:string |
| http://purl.uniprot.org/citations/16236725 | http://purl.uniprot.org/core/author | "Tomiyama Y."xsd:string |
| http://purl.uniprot.org/citations/16236725 | http://purl.uniprot.org/core/author | "Fujii J."xsd:string |
| http://purl.uniprot.org/citations/16236725 | http://purl.uniprot.org/core/author | "Honke K."xsd:string |
| http://purl.uniprot.org/citations/16236725 | http://purl.uniprot.org/core/author | "Asahi M."xsd:string |
| http://purl.uniprot.org/citations/16236725 | http://purl.uniprot.org/core/author | "Shapiro S.D."xsd:string |