Gene regulation by mechanotransduction in fibroblasts
Bibliographic record
Abstract
Mechanical forces are important for connective tissue homeostasis. How do fibroblasts sense mechanical stress and how do they translate this information into an adaptive remodeling of the extracellular matrix (ECM)? Tenascin-C is rapidly induced in vivo by loading muscles and in vitro by stretching fibroblasts. Regulation of tenascin-C expression by mechanical signals occurs at the transcriptional level. Integrin receptors physically link the ECM to the cytoskeleton and act as force transducers: intracellular signals are triggered when integrins engage with ECM, and later when forces are applied. We found that cyclic strain does not induce tenascin-C messenger ribonucleic acid (mRNA) in fibroblasts lacking the beta1-integrin chain. An important link in integrin-dependent mechanotransduction is the small guanosine 5'-triphosphatase. RhoA and its target kinase, ROCK. In fibroblasts, cyclic strain activates RhoA and thereby induces ROCK-dependent actin assembly. Interestingly, tenascin-C mRNA induction by cyclic strain was suppressed by relaxing the cytoskeleton with a ROCK inhibitor or by actin depolymerization. Conversely, chemical activators of RhoA enhanced the effect of strain both on actin dynamics and on tenascin-C expression. Thus, RhoA/ROCK-controlled actin dynamics are required for the induction of specific ECM genes by mechanical stress. These findings have implications for the understanding of regeneration and for tissue engineering.
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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) | 0.001 | 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 | 0.001 | 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".