The effect of decorin and biglycan on human airway smooth muscle cell proliferation, apoptosis and attachment
Bibliographic record
Abstract
Changes in extracellular matrix (ECM) deposition along with increases in airway smooth muscle (ASM) mass are characteristic features of airway remodeling which contribute to asthma pathophysiology. Modifications in ECM include increased collagen deposition and altered proteoglycans (PGs) levels. While biglycan, a small leucine-rich PG (SLRP), deposition is generally increased, changes in decorin, another SLRP, are more variable. The interaction between the cell and the surrounding ECM triggers numerous cellular responses, which modulate functions such as survival, proliferation and differentiation. Since decorin and biglycan are known to influence cell behaviour in various types of cells, we hypothesized that these molecules would affect human airway smooth muscle cell (HASMC) function. We sought to determine the effects of decorin and biglycan on HASMC proliferation, apoptosis and attachment, and to explore the putative mechanisms responsible for these effects. Collagen type I was used as a control.Culture on a decorin matrix caused a decrease in HASMC number, which was attributed to a decrease in proliferation and an increase in apoptosis. Culture on biglycan caused an initial decrease in cell number that was not sustained. Collagen caused a significant increase in cell number. Neither biglycan nor collagen caused changes in proliferation or apoptosis. Subsequent experiments showed that cell anchorage to decorin and biglycan matrices caused abnormal focal adhesion and cytoskeletal organization, as well as, increases in alpha2 integrin protein levels as compared to cells seeded on collagen or plastic. To assess integrin activation, focal adhesion kinase (FAK) protein levels and activation were measured. FAK levels were significantly decreased compared to cells cultured on plastic or collagen I, but activation levels were unchanged.These studies demonstrate that PGs have differential effects on HASMC growth. Whereas decorin reduces ASM proliferation and increases apoptosis, biglycan has no effect. Cell-matrix adhesions were irregular in HASMCs seeded on decorin or biglycan compared to cells on collagen I or plastic. Decreases in decorin in the asthmatic airway wall, as observed in fatal asthma cases, may permit more exuberant ASM hyperplasia, suggesting that decorin's presence could serve a protective role by modulating the increase in ASM mass in asthma.
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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".