Decorin Is a Novel VEGFR-2 Binding Antagonist for the Human Extravillous Trophoblast.
Bibliographic record
Abstract
Extravillous trophoblast (EVT) cells of the human placenta invade the uterine decidua and its arteries to nourish the fetus. We identified two decidua-derived molecules TGF-β, and a TGF-β binding small leucine-rich proteoglycan decorin (DCN) which independently controlled EVT cell proliferation, migration and invasiveness. Multiple tyrosine kinase receptors EGF-R, IGFR-1 and VEGFR-2 were shown to mediate these DCN actions. Since DCN binding to VEGFR-2 has never been reported before, we explored the characteristics of this binding and the identity of VEGFR-2 binding sites of DCN in our human first trimester EVT cell line HTR-8/SVneo; and whether this binding antagonised VEGF-induced cellular proliferation and migration. DCN binding to VEGFR-2 in EVT cell lysate or pure recombinant VEGFR-2/Fc chimera was shown with far-western blotting and co-immunoprecipitation. VEGFR-2 lacking Human Embryonic kidney (HEK) cells were used as a negative control. The binding was abrogated with a VEGFR-2 blocking antibody indicating an overlap between the ligand-binding and the DCN-binding domains of VEGFR-2. 125I-labeled VEGF-E (a VEGFR-2 specific ligand) bound to intact EVT cells, with a Kd of 566 pM, and DCN displaced this binding with a Ki of 5.78nM, indicating a 10 fold lower affinity of DCN for VEGFR-2. DCN peptide fragments in the leucine-rich repeat (LRR)-5 domain that preferentially blocked DCN-VEGFR-2 binding in EVT cell proteins also blocked VEGF-induced EVT cell proliferation and migration, indicative of functional VEGFR-2 binding sites of DCN. Our novel findings of DCN as an antagonistic ligand for VEGFR-2 and its ability to block EVT cell migration has implications for pathobiology of preeclampsia, a trophoblast hypo-invasive disorder in pregnancy, and explains its anti-angiogenic role. (Supported by funds from the Canadian Institutes of Health Research to PKL) (poster)
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".