FGFR-1 regulates angiogenesis through cytokines interleukin-4 and pleiotrophin
| Autor: | Sofie Mellberg, Peetra U. Magnusson, Anna Dimberg, Lena Claesson-Welsh, Agneta Lukinius |
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| Rok vydání: | 2007 |
| Předmět: |
Pathology
medicine.medical_specialty animal structures Transcription Genetic Endothelium Angiogenesis Immunology Neovascularization Physiologic Embryoid body Biology Fibroblast growth factor Pleiotrophin Biochemistry Mice medicine Animals Receptor Fibroblast Growth Factor Type 1 Cell Shape Cells Cultured Mice Knockout Stem Cells Fibroblast growth factor receptor 1 Teratoma Cell Biology Hematology Cell biology Endothelial stem cell medicine.anatomical_structure Gene Expression Regulation Fibroblast growth factor receptor embryonic structures Cytokines Endothelium Vascular Interleukin-4 biological phenomena cell phenomena and immunity Carrier Proteins |
| Zdroj: | Blood. 110:4214-4222 |
| ISSN: | 1528-0020 0006-4971 |
| Popis: | The role of fibroblast growth factors (FGFs) in blood vessel formation has remained unclear. We used differentiating stem-cell cultures (embryoid bodies) and teratomas to show that FGF receptor-1 (FGFR-1) exerts a negative regulatory effect on endothelial cell function in these models. Embryoid bodies lacking expression of FGFR-1 as a result of gene targeting (Fgfr-1−/−) displayed increased vascularization and a distinct, elongated vessel morphology. Teratomas derived from FGFR-1–deficient stem cells were characterized by an increased growth rate and abundant, morphologically distinct vessels. Transmission electron microscopy of the Fgfr-1−/− teratomas showed a compact and voluminous but functional endothelium, which anastomosed with the host circulation. The increased vascularization and altered endothelial cell morphology was dependent on secreted factor(s), based on the transfer of the Fgfr-1−/− vascular phenotype by conditioned medium to Fgfr-1+/− embryoid bodies. Antibody and transcript arrays showed down-regulation of interleukin-4 (IL-4) and up-regulation of pleiotrophin in Fgfr-1−/− embryoid bodies, compared with the heterozygous cultures. We used neutralizing antibodies to show that IL-4 and pleiotrophin act as negative and positive angiogenic regulators, respectively. We conclude that FGFR-1 negatively regulates endothelial cell function by altering the balance of modulatory cytokines. |
| Databáze: | OpenAIRE |
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