The yes-associated protein-1 (YAP1) inhibitor celastrol suppresses the ability of transforming growth factor β to activate human gingival fibroblasts
Bibliographic record
Abstract
OBJECTIVE: To determine whether celastrol, an inhibitor of the mechanosensitive transcriptional cofactor yes-associated protein-1 (YAP1), impairs the ability of TGFβ1 to stimulate fibrogenic activity in human gingival fibroblast cell line. DESIGN: Human gingival fibroblasts were pre-treated with celastrol or DMSO followed by stimulation with or without TGFβ1 (4 ng/ml). We then utilized bulk RNA sequencing (RNAseq), real-time polymerase chain reaction (RT-PCR), Western blot, immunofluorescence, cell proliferation assays to determine if celastrol impaired TGFβ1-induced responses in a human gingival fibroblast cell line. RESULTS: Celastrol impaired the ability of TGFβ1 to induce expression of the profibrotic marker and mediator CCN2. Bulk RNAseq analysis of gingival fibroblasts treated with TGFβ1, in the presence or absence of celastrol, revealed that celastrol impaired the ability of TGFβ1 to induce mRNA expression of genes within extracellular matrix, wound healing, focal adhesion and cytokine/Wnt signaling clusters. RT-PCR analysis of extracted RNAs confirmed that celastrol antagonized the ability of TGFβ1 to induce expression of genes anticipated to contribute to fibrotic responses. Celastrol also reduced gingival fibroblast proliferation, and YAP1 nuclear localization in response to TGFβ1. CONCLUSION: YAP1 inhibitors such as celastrol could be used to impair pro-fibrotic responses to TGFβ1 in human gingival fibroblasts.
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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".