EGFL7 ligates αvβ3 integrin to enhance vessel formation
| العنوان: | EGFL7 ligates αvβ3 integrin to enhance vessel formation |
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| المؤلفون: | Khader Awwad, Benno Jungblut, Michel Mittelbronn, Chinmoy Patra, Michael K. E. Schäfer, Emmanouil Chavakis, Felix B. Engel, Mirko H. H. Schmidt, Jeannette Meister, Jan Baumgart, Nevenka Dudvarski Stanković, Ingrid Fleming, Iva Nikolic, Frank Bicker, Johannes A. Eble, Stefanie Dimmeler, Helene Braun, Serge C. Thal, Kirsten Simon, Patrick N. Harter, Karl H. Plate |
| المصدر: | Blood. 121:3041-3050 |
| بيانات النشر: | American Society of Hematology, 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | EGF Family of Proteins, Embryo, Nonmammalian, Angiogenesis, Amino Acid Motifs, Immunology, Integrin, Gene Expression, Mice, Nude, Endothelial Growth Factors, Biochemistry, Collagen receptor, Mice, Cell Movement, Cell Adhesion, Human Umbilical Vein Endothelial Cells, medicine, Animals, Humans, Immunoprecipitation, Phosphorylation, Zebrafish, biology, Reverse Transcriptase Polymerase Chain Reaction, Chemistry, Calcium-Binding Proteins, Infarction, Middle Cerebral Artery, Venous plexus, Cell Biology, Hematology, Integrin alphaVbeta3, Immunohistochemistry, Extracellular Matrix, Cell biology, Endothelial stem cell, HEK293 Cells, medicine.anatomical_structure, Integrin alpha M, biology.protein, Blood Vessels, RNA Interference, Integrin, beta 6, Protein Binding, Blood vessel |
| الوصف: | Angiogenesis, defined as blood vessel formation from a preexisting vasculature, is governed by multiple signal cascades including integrin receptors, in particular integrin αVβ3. Here we identify the endothelial cell (EC)-secreted factor epidermal growth factor-like protein 7 (EGFL7) as a novel specific ligand of integrin αVβ3, thus providing mechanistic insight into its proangiogenic actions in vitro and in vivo. Specifically, EGFL7 attaches to the extracellular matrix and by its interaction with integrin αVβ3 increases the motility of EC, which allows EC to move on a sticky underground during vessel remodeling. We provide evidence that the deregulation of EGFL7 in zebrafish embryos leads to a severe integrin-dependent malformation of the caudal venous plexus, pointing toward the significance of EGFL7 in vessel development. In biopsy specimens of patients with neurologic diseases, vascular EGFL7 expression rose with increasing EC proliferation. Further, EGFL7 became upregulated in vessels of the stroke penumbra using a mouse model of reversible middle cerebral artery occlusion. Our data suggest that EGFL7 expression depends on the remodeling state of the existing vasculature rather than on the phenotype of neurologic disease analyzed. In sum, our work sheds a novel light on the molecular mechanism EGFL7 engages to govern physiological and pathological angiogenesis. |
| تدمد: | 1528-0020 0006-4971 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c1714d1d0a170b41918067e35addb39bTest https://doi.org/10.1182/blood-2011-11-394882Test |
| رقم الانضمام: | edsair.doi.dedup.....c1714d1d0a170b41918067e35addb39b |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15280020 00064971 |
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