INTEGRIN SIGNALING DOES NOT MEDIATE THE INCREASE IN ZIF268 MRNA DURING CONTRACTILE ACTIVITY
Bibliographic record
Abstract
Integrins may be important mechanotransduction molecules during muscle contraction. To evaluate the role of integrins in mediating changes in muscle phenotype in response to contractile activity, mouse C2C12 cells were stimulated in vitro at 5 Hz for up to 90 minutes. The mRNA level of the transcription factor Zif268 was used as an indicator of a rapid adaptive response, since its mRNA is rapidly up-regulated by contractile activity, and also by treatment with the calcium ionophore A23187. The effect of A23187 is abolished in the presence of the MEK inhibitor PD098059, suggesting that extracellular signal-regulated kinase (ERK-1 and 2) activation is involved. Zif268 mRNA increased 2.5-fold after 30 minutes of stimulation. To evaluate whether the response was mediated by integrin signaling, cells were plated on fibronectin and treated with either water or the disintegrin echistatin (20 nM) to inhibit integrin activation. The stimulation-induced rise in zif268 mRNA was not inhibited by echistatin. The absence of integrin signaling was also substantiated by the lack of a contractile activity effect on focal adhesion kinase (FAK) tyrosine phosphorylation. Inhibition of MEK, a downstream target of FAK, with PD098059 reduced the control level of zif268 mRNA expression, but did not inhibit the contractile activity-induced increase. Since zif268 has multiple serum response elements in its promoter, we also evaluated the mRNA response of serum response factor (SRF). No effect of contractile activity was observed after 30 minutes. Transfection of cells with the zif268 promoter-CAT construct illustrated that contractile activity did not increase zif268 mRNA via transcriptional activation. These data suggest that 1) zif268 mRNA is induced by changes in mRNA stability rather than by transcription, 2) integrin signaling is not activated in this model of contractile activity, and 3) that neither integrins or ERK-1/2 are involved in stimulating the increase in zif268 mRNA in response to contractile activity.
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".