Zeb2: A novel regulator of cardiac fibroblast to myofibroblast transition
Bibliographic record
Abstract
Cardiac fibroblast to myofibroblast phenoconversion is a critical step in cardiovascular disease progression. Myofibroblasts contribute to cardiac fibrosis by chronic extracellular matrix remodelling and scar formation which subsequently results in myocardial stiffening, impaired contraction, cardiac dysfunction and eventually to heart failure. Previously we showed that Meox2, a homeobox transcription factor, is highly expressed in fibroblasts compared to myofibroblasts. As well we demonstrated that Meox2 can inhibit myofibroblast phenoconversion by down‐regulating a set of myofibroblast markers. Here we report for the first time that Zeb2, a repressor of Meox2 and an epithelial‐mesenchymal transition inducer, may play a crucial role during this phenoconversion process. Using rat cardiac fibroblasts, we have shown that Zeb2 overexpression causes an up‐regulation of a set of myofibroblast markers‐ SMemb, ED‐A fibronection and α‐SMA. We showed that Zeb2 is highly expressed in myofibroblast nuclei whereas it is only minimally expressed in fibroblasts as observed by immunoblotting and confocal microscopy. Moreover, ectopic Zeb2 expression results in a less migratory phenotype‐ characteristic of mature myofibroblasts. We also showed that Zeb2 overexpression represses Meox2 expression in endothelial cells. We will investigate the role of Zeb2 in myofibroblast proliferation, apoptosis and function in vitro . Thus findings from our study will provide insight to understand the mechanism behind myofibroblast phenoconversion and may provide a basis for developing a Zeb2‐based novel anti‐fibrotic drug in the future.
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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".