Impaired endothelial shear stress induces podosome assemblyviaVEGF up‐regulation
| Autor: | Kai Michael Schubert, Theres Fey, Ulrich Pohl, Andreas Dendorfer, Holger Schneider, Evelyn Fein, Eike Christian Kleinert |
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| Rok vydání: | 2016 |
| Předmět: |
Male
Vascular Endothelial Growth Factor A 0301 basic medicine Podosome Angiogenesis Down-Regulation Motility p38 Mitogen-Activated Protein Kinases Biochemistry Mice 03 medical and health sciences Cell Movement Stress Physiological Genetics Shear stress Animals Humans Cytoskeleton Molecular Biology Chemistry Endothelial Cells Kinase insert domain receptor Vascular Endothelial Growth Factor Receptor-2 Matrix Metalloproteinases Up-Regulation Cell biology Mice Inbred C57BL Vascular endothelial growth factor A src-Family Kinases 030104 developmental biology Gene Expression Regulation Podosomes Podosome assembly Biotechnology |
| Zdroj: | The FASEB Journal. 30:2755-2766 |
| ISSN: | 1530-6860 0892-6638 |
| DOI: | 10.1096/fj.201500091r |
| Popis: | Podosomes are dynamic cytoskeletal membrane structures with local adhesive and proteolytic activity. They are critically involved in angiogenesis and vascular adaptive growth. Here, we studied in HUVECs and murine small vessels whether shear stress controls podosome assembly and local proteolytic activity. Podosomes were characterized by immunohistochemistry, and their proteolytic activity was assessed as degradation imprints in fluorescent gelatin that was used as growth substrate. Compared with controls (10 dyn/cm(2)), the number of podosomes formed per time was doubled when cells were exposed to low shear stress (0.3 dyn/cm(2)) or even increased 5-fold under static conditions. This was a result of an enhanced expression of VEGF after reduction of shear stress. Consequently, enhanced podosome formation could be prevented by a VEGF receptor antagonist as well by interruption of VEGF signaling via inhibition of PI3K, Src, or p38. Increase of podosome assembly went along with significantly augmented cell motility. In vivo experiments in mouse arteries confirmed increased endothelial podosome numbers when shear stress was abolished by vessel occlusion. We conclude that shear stress, by reducing VEGF release, inhibits podosome assembly. Hence, endothelial cell-mediated matrix proteolysis and migratory activity are inhibited, thereby stabilizing the structure of the vessel wall.-Fey, T., Schubert, K. M., Schneider, H., Fein, E., Kleinert, E., Pohl, U., Dendorfer, A. Impaired endothelial shear stress induces podosome assembly via VEGF up-regulation. |
| Databáze: | OpenAIRE |
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