Syndecan-4 regulates extravillous trophoblast migration by coordinating protein kinase C activation
Bibliographic record
Abstract
Extravillous trophoblast (EVT) invasion is an essential component of human placentation. Poor EVT invasion is associated with obstetrical complications including preeclampsia. Integration of cues from the extracellular environment is required for directional EVT invasion, but how EVTs coordinate responses to these cues is not well understood. Syndecan-4 (SDC4) is a transmembrane heparan sulfate proteoglycan that binds to, and modulates the activity of, many extracellular proteins implicated in placental development. Therefore, we determined the functional importance of SDC4 for EVT invasion. We found that SDC4 is expressed by a first trimester EVT line (HTR8), and in EVTs in placenta throughout pregnancy, with higher expression during early pregnancy than at term. Higher expression was also observed in placentas from preeclampsia compared to normotensive pregnancies. SDC4-deficient HTR8 EVTs exhibited reduced migration and Matrigel-based invasion, both under basal conditions and following exposure to basic fibroblast growth factor and heparin-binding epidermal growth factor. SDC4-deficient HTR8 EVTs also showed reduced protein kinase C-alpha (PKCα) and AKT phosphorylation. SDC4 directly bound to activated PKCα in EVTs, and inhibition of PKCα decreased EVT invasion and migration. Our findings reveal an essential role of SDC4 as a regulator of EVT motility, in part through coordination of PKCα activation.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| 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) | 0.001 | 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 source (direct Gemma or distilled Codex), 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".