Scleraxis works synergistically with Smads to regulate collagen gene expression
Bibliographic record
Abstract
Elevated type I collagen expression in cardiac fibrosis impairs heart function. We have shown that the transcription factor scleraxis (Scx) is expressed by cardiac fibroblasts and myofibroblasts, and is sufficient to regulate human collagen Iα2 ( COLIα2 ) expression. Here we studied the interaction of Scx with the fibrotic Smad signaling pathway. We identified Scx binding sites (E‐boxes) within the COLIα2 proximal gene promoter, examined promoter occupancy by Scx using ChIP assay, and measured promoter activation by Scx and/or Smads via luciferase gene reporter assays. Scx augmented TGF‐β 1 transactivation of the promoter. Scx and Smad3 synergistically up‐regulated COLIα2 promoter transactivation. Mutation of the promoter Smad binding element significantly reduced transactivation by Scx. A similar effect of E‐box mutations on Smad3‐mediated activation was also observed, suggesting that cross‐talk in these pathways is required for maximal gene activity. Scx expression was up‐regulated by Smad3 and down‐regulated by Smad7, further supporting cross‐pathway signaling. A dominant negative Scx mutant completely abrogated COLIα2 gene expression by TGF‐β 1 . Our results indicate that Scx and Smads synergistically co‐regulate collagen gene expression, and that interference with this interaction may represent a novel avenue for anti‐fibrotic therapy development. Supported by CIHR and MHRC.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 | 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".