Cell proliferating effect of latent transforming growth factor‐β1 is cell membrane dependent
Bibliographic record
Abstract
The mechanism of in vivo activation of transforming growth factor-beta1 (TGF-beta1), which is critical to its role in many physiological and pathological conditions, is not fully understood. To explore the mechanism by which dermal fibroblasts respond to latent TGF-beta1 directly, the efficacy of either latent TGF-beta1 (LTGF-beta1) alone or LTGF-beta1 plus cell membranes isolated from fibroblasts, mink lung, and one skin-related (Sk23) and two skin-unrelated (U251 and D54MG) transformed cell lines was examined using the mink lung epithelial cell (Mv1Lu) inhibition assay. As a source of LTGF-beta1, PA317 cells were transfected with previously constructed pLin-TGF-beta1 or pLin vectors with no TGF-beta1 insert. LTGF-beta1 expressing PA317 cells were then enriched by growth in the presence of 0.5 mg G-418 for 6-10 days. Eight out of 53 colonies of cells expressing high levels of LTGF-beta1 were selected and their conditioned media were removed after 3 days and used to evaluate the latency and bioactivity of TGF-beta1 using ELISA and Mv1Lu growth inhibition assay, respectively. The level of TGF-beta1 was 19-fold greater (21.4 +/- 0.4 vs. 1.1 +/- 0.2 ng/ml) in conditioned medium derived from pLin-TGF-beta1 transfected cells than that of control. These conditioned media were then used for the subsequent cell proliferating experiments. The results showed that latent TGF-beta1, which proved to be inactive in an Mv1Lu inhibition assay, significantly stimulates fibroblast cell proliferation compared to that of control in a dose-dependent fashion. In another set of experiments, cells were treated with either active (acidified/neutralized) or latent TGF-beta1 and the results showed a significant increase in cell proliferation in response to low concentrations of active TGF-beta1. However, high concentrations of active TGF-beta1 markedly suppressed fibroblast proliferation. These dual effects were in contrast to a steady increase in fibroblast proliferation found in response to latent TGF-beta1. To explore why LTGF-beta1 has a differential proliferating effect on epithelial and fibroblast cell proliferation, cell membranes from these cells were isolated and incubated with PA317-conditioned medium containing LTGF-beta1 and then added to mink lung cells. Only isolated fibroblast cell membranes incubated with LTGF-beta1 inhibited Mv1Lu cells. To examine whether the LTGF-beta1 cell proliferating activity is unique to dermal fibroblasts or is a general phenomenon, in similar experimental conditions cell membranes from several cell lines, U251, D54MG, and SK23, were isolated, incubated with LTGF-beta1, and then added to an Mv1Lu inhibition assay. The proliferation of Mv1Lu epithelial cells was significantly (1547 +/- 269 vs. 3568 +/- 23) inhibited with SK23, but not U251 cell membranes plus LTGF-beta1 relative to that of control. The inhibitory effect of SK23 plus LTGF-beta1 was cell membrane dose-dependent. In conclusion, the result of this study shows that LTGF-beta1 may directly modulate cell proliferation of those cells that possess a cell membrane associated LTGF-beta1 activation mechanism.
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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".