Abrogation of apoptosis through PDGF-BB-induced sulfated glycosaminoglycan synthesis and secretion
Bibliographic record
Abstract
Platelet-derived growth factor (PDGF)-BB-stimulated glycosaminoglycan (GAG) synthesis/secretion in fetal lung fibroblasts is dependent on sequential activation of the PDGF beta-receptor, phosphatidylinositol 3-kinase (PI3K), the serine/threonine kinase Akt-1,2, and the GTPase Rab3D. Because the Akt pathway has been implicated in cell survival mechanisms, we investigated whether the pathway regulating GAG synthesis/secretion was antiapoptotic. PDGF-BB treatment protected fetal lung fibroblasts against serum starvation-induced apoptosis, whereas wortmannin, an inhibitor of PI3K, abrogated this protective effect. Transfection of constitutively active Akt into fetal lung fibroblasts also safeguarded the cells from apoptosis induced by serum starvation. To determine whether the antiapoptotic response was due, at least in part, to GAGs, we treated lung fibroblasts with beta-D-xyloside as well as with topically applied GAGs, specifically those produced by fetal lung fibroblasts. beta-D-xyloside increased GAG synthesis/secretion and diminished apoptosis. Application of sulfated GAGs, chondroitin sulfate, and heparan sulfate, but not nonsulfated hyaluronan, also resulted in diminished apoptosis. Moreover, topically applied sulfated GAGs increased Bcl-associated death promoter phosphorylation and diminished caspase-3 and -7 cleavage, indicating an antiapototic response. These data are compatible with the PDGF-BB-GAG signaling pathway regulating programmed fibroblast death in the fetal lung.
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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".