Редактирование: FGF4 (раздел)

==Publications==

{{medline-entry
|title=Negative autoregulation of fibroblast growth factor receptor 2 expression characterizing cranial development in cases of Apert (P253R mutation) and Pfeiffer (C278F mutation) syndromes and suggesting a basis for differences in their cranial phenotypes.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/11596961
|abstract=Heterogeneous mutations in the fibroblast growth factor receptor 2 gene ([[FGFR2]]) cause a range of craniosynostosis syndromes. The specificity of the Apert syndrome-affected cranial phenotype reflects its narrow mutational range: 98% of cases of Apert syndrome result from an Ser252Trp or Pro253Arg mutation in the immunoglobulin-like (Ig)IIIa extracellular subdomain of [[FGFR2]]. In contrast, a broad range of mutations throughout the extracellular domain of [[FGFR2]] causes the overlapping cranial phenotypes of Pfeiffer and Crouzon syndromes and related craniofacial dysostoses. In this paper the expression of [[FGFR1]], the IgIIIa/c and IgIIIa/b isoforms of [[FGFR2]], and [[FGFR3]] is investigated in Apert syndrome (P253R mutation)- and Pfeiffer syndrome (C278F mutation)-affected fetal cranial tissue and is contrasted with healthy human control tissues. Both [[FGFR1]] and [[FGFR3]] are normally expressed in the differentiated osteoblasts of the periosteum and osteoid, in domains overlapped by that of [[FGFR2]], which widely include preosseous cranial mesenchyme. Expression of [[FGFR2]], however, is restricted to domains of advanced osseous differentiation in both Apert syndrome- and Pfeiffer syndrome-affected cranial skeletogenesis in the presence of fibroblast growth factor (FGF)2, but not in the presence of [[FGF4]] or [[FGF7]]. Whereas expression of the [[FGFR2]]-IgIIIa/b (KGFR) isoform is restricted in normal human cranial osteogenesis, there is preliminary evidence that KGFR is ectopically expressed in Pfeiffer syndrome-affected cranial osteogenesis. Contraction of the [[FGFR2]]-IgIIIa/c (BEK) expression domain in cases of Apert syndrome- and Pfeiffer syndrome-affected fetal cranial ossification suggests that the mutant activation of this receptor, by ligand-dependent or ligand-independent means, results in negative autoregulation. This phenomenon, resulting from different mechanisms in the two syndromes, offers a model by which to explain differences in their cranial phenotypes.
|mesh-terms=* Acrocephalosyndactylia
* Aging
* Embryonic and Fetal Development
* Fetus
* Homeostasis
* Humans
* Infant
* Mutation
* Osteogenesis
* Phenotype
* Receptor Protein-Tyrosine Kinases
* Receptor, Fibroblast Growth Factor, Type 1
* Receptor, Fibroblast Growth Factor, Type 2
* Receptors, Fibroblast Growth Factor
* Skull

|full-text-url=https://sci-hub.do/10.3171/jns.2001.95.4.0660
}}
{{medline-entry
|title=Attenuation of FGF signalling in mouse beta-cells leads to diabetes.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/11130726
|abstract=Fibroblast growth factor (FGF) signalling has been implicated in patterning, proliferation and cell differentiation in many organs, including the developing pancreas. Here we show that the FGF receptors (FGFRs) 1 and 2, together with the ligands [[FGF1]], [[FGF2]], [[FGF4]], [[FGF5]], [[FGF7]] and [[[[FGF1]]0]], are expressed in adult mouse beta-cells, indicating that FGF signalling may have a role in differentiated beta-cells. When we perturbed signalling by expressing dominant-negative forms of the receptors, [[FGFR1]]c and FGFR2b, in the pancreas, we found that that mice with attenuated [[FGFR1]]c signalling, but not those with reduced FGFR2b signalling, develop diabetes with age and exhibit a decreased number of beta-cells, impaired expression of glucose transporter 2 and increased proinsulin content in beta-cells owing to impaired expression of prohormone convertases 1/3 and 2. These defects are all characteristic of patients with type-2 diabetes. Mutations in the homeobox gene Ipf1/Pdx1 are linked to diabetes in both mouse and human. We also show that Ipf1/Pdx1 is required for the expression of [[FGFR1]] signalling components in beta-cells, indicating that Ipf1/Pdx1 acts upstream of [[FGFR1]] signalling in beta-cells to maintain proper glucose sensing, insulin processing and glucose homeostasis.
|mesh-terms=* Aging
* Animals
* Blood Glucose
* Diabetes Mellitus, Experimental
* Diabetes Mellitus, Type 2
* Fibroblast Growth Factors
* Glucose Transporter Type 1
* Glucose Transporter Type 2
* Homeodomain Proteins
* Humans
* Insulin
* Islets of Langerhans
* Mice
* Mice, Transgenic
* Monosaccharide Transport Proteins
* Pancreas
* Receptor Protein-Tyrosine Kinases
* Receptor, Fibroblast Growth Factor, Type 1
* Receptor, Fibroblast Growth Factor, Type 2
* Receptors, Fibroblast Growth Factor
* Signal Transduction
* Trans-Activators

|full-text-url=https://sci-hub.do/10.1038/35048589
}}
{{medline-entry
|title=Hyperplasia and impaired involution in the mammary gland of transgenic mice expressing human [[FGF4]].
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/11146552
|abstract=Fgf4, a member of the fibroblast growth factor family, is frequently amplified in a variety of human cancers, however, its expression in neoplastic tissues is rarely detectable. This makes uncertain its involvement in tumour aetiology, although several in-vitro studies link Fgf4 overexpression to malignant transformation and metastatization of culture cells. We generated a transgenic mouse model in which the whey acidic protein (WAP) promoter directs expression of human Fgf4 to mammary tissues during late pregnancy and throughout lactation, with the purpose of studying the involvement of this growth factor in mammary tumorigenesis. Expression of the transgene was specifically detected in lobular-alveolar cells of lactating mammary glands that, by histological analysis, displayed hyperplastic areas and a disorganized structure. This was accompanied by an increased number of red blood cells and expression, in alveolar epithelial cells, of the vascular endothelial growth factor, which is absent in wild type controls. The most striking effect caused by [[FGF4]] overexpression was on the remodelling of mammary tissue at the end of lactation. Indeed, transgenic animals showed a delayed involution of the gland due to a dramatic reduction in the overall number of apoptotic cells, which are normally present in the organ after weaning. Nevertheless, none of the animals examined developed neoplastic lesions of the mammary gland even after several pregnancies and at old age. Our work represents the first in-vivo demonstration of the anti-apoptotic and angiogenic properties of [[FGF4]].
|mesh-terms=* Aging
* Animals
* Apoptosis
* Blotting, Western
* Cell Transformation, Neoplastic
* Endothelial Growth Factors
* Epithelial Cells
* Female
* Fibroblast Growth Factor 4
* Fibroblast Growth Factors
* Gene Expression Regulation
* Humans
* Hyperplasia
* Immunohistochemistry
* Lactation
* Lymphokines
* Mammary Glands, Animal
* Mammary Neoplasms, Animal
* Mice
* Mice, Transgenic
* Milk Proteins
* Neovascularization, Pathologic
* Phenotype
* Pregnancy
* Promoter Regions, Genetic
* Proto-Oncogene Proteins
* RNA, Messenger
* Transgenes
* Vascular Endothelial Growth Factor A
* Vascular Endothelial Growth Factors

|full-text-url=https://sci-hub.do/10.1038/sj.onc.1204011
}}