|
| Status |
Public on Mar 04, 2019 |
| Title |
Rigidity and inflammatory responses of interconnected endothelial cells are stimulated by rhodocetin-αβ via the neuropilin-1-MET-axis |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
Using the snake venom component rhodocetin-αβ (RCαβ), we elucidated how neuropilin-1 (NRP1)-dependent signaling of the hepatocyte growth factor/scatter factor (HGF/SF) receptor, MET, modulates endothelial cell-cell contacts, cell tension, and consequently nuclear factor kappa B (NFκB)-triggered proinflammatory response.
We show that RCαβ in confluent ECs, also if exposed to fluid shear forces, induces loss of force-transmitting focal adhesions and a change of vinculin localization from cell-matrix contacts to cell-cell contacts. Together with RhoA activation, this enhances force transmission via intercellular contacts and raises cell rigidity within the EC monolayer. Presumably due to the combined effects of redirecting forces and NRP1-MET-signaling, RCαβ, in contrast to HGF, activates NFκB and thus a distinct set of genes. Transcriptome analysis revealed an RCαβ-induced activation of the intercellular adhesion molecule-1 (ICAM1), of other markers of EC activation and of several inflammatory cytokines, resulting in increased pericellular permeability and enhanced leukocyte attachment and transmigration.
|
| |
|
| Overall design |
HUVECs from passage 1 were seeded on collagen I-coated plates. Fluid shear stress experiments were performed in a cone plate-based BioTechFlow system. After treatment with or without 200 nM RCαβ, statically incubated and shear-subjected cells were collected and analyzed by MFTServices. To compare the genes up- and downregulated by HGF or RCαβ, we stimulated ECs with 200 nM RCαβ or 200 ng/ml HGF under static condition for 8 hour. Cells then were collected and analyzed by MFTServices.
|
| |
|
| Contributor(s) |
Eble JA, Rezaei M, Matthes J |
| Citation(s) |
30692210 |
| Submission date |
Oct 16, 2018 |
| Last update date |
Jun 19, 2019 |
| Contact name |
Jakob Admard |
| Organization name |
Universitätsklinikum Tübingen
|
| Department |
Institut für Medizinische Genetik und Angewandte Genomik
|
| Street address |
Calwerstr. 7
|
| City |
Tübingen |
| ZIP/Postal code |
72076 |
| Country |
Germany |
| |
|
| Platforms (2) |
| GPL570 |
[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array |
| GPL13667 |
[HG-U219] Affymetrix Human Genome U219 Array |
|
| Samples (19)
|
|
| Relations |
| BioProject |
PRJNA496601 |
Less...
More...