Decorin Inhibits Human Trophoblast Migration by Interfering with VEGF-Induced p38 MAPK and ERK1/2 Activation.
Bibliographic record
Abstract
The human placenta is an invasive tumour-like organ that invades the uterine endometrium and its vasculature to establish sufficient fetal-maternal exchange. A subpopulation of trophoblast cells, known as extravillous trophoblasts (EVT), grows out of the anchoring villi, invades the uterine decidua and remodels the uterine arteries. During this process, EVT cells adopt an endovascular phenotype and replace the endothelium of the arteries transforming these normally small muscular arteries into large, non-contractile and flaccid vessels. This transformation allows for unimpeded placental perfusion necessary for the adequate exchange of crucial molecules between the fetal and maternal circulations. We have previously shown that EVT cell invasion is negatively regulated by a decidua-derived, small leucine rich proteoglycan, decorin (DCN). Decorin was shown to bind vascular endothelial growth factor receptor (VEGFR)-2 on the first trimester EVT cell line, HTR-8/SVneo. In this study, we examined whether decorin binding to VEGFR-2 antagonises VEGF-induced EVT cell migration and endothelial-like tube formation on matrigel (an in vitro model of the endovascular phenotype); and if so, the underlying signalling mechanisms behind this inhibition. To study migration, cells were pre-treated with decorin and seeded in the upper chamber of a transwell insert, where VEGF121 was placed in the bottom chamber. Decorin inhibited VEGF-induced tube formation and migration in a concentration-dependent manner. Western blot analysis revealed that VEGF stimulated p38 Mitogen-Activated Protein Kinase (MAPK) as well as MAPK p42/p44 (ERK1/2) activation and that these activation events could be blocked by decorin. Inhibitors for p38 MAPK and ERK1/2 (SB203580 and U0126, respectively) also inhibited VEGF-induced migration. These results suggest that decorin inhibits VEGF-induced migration by interfering with VEGF induced p38 and ERK1/2 activation. Our novel finding of decorin as an antagonistic ligand for VEGFR-2 as well as its ability to block migration and acquisition of an endovascular phenotype has implications for the pathobiology of preeclampsia, a hypo-invasive trophoblast disorder in pregnancy. (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".