α11 integrin stimulates myofibroblast differentiation in diabetic cardiomyopathy
Why this work is in the frame
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Bibliographic record
Abstract
AIMS: Diabetic cardiomyopathy is characterized by the production of a disorganized fibrotic matrix in the absence of coronary atherosclerosis and hypertension. We examined whether adhesion of cardiac fibroblasts to glycated collagens mediates the differentiation of pro-fibrotic myofibroblasts, which may contribute to cardiac fibrosis. METHODS AND RESULTS: By microarray, we found that methylglyoxal-treated collagen selectively enhanced α11 integrin expression in human cardiac fibroblasts, while levels of other collagen-binding integrins (α1, α2, and α10) were unchanged. Similar increases in α11 integrin mRNA and protein expression were observed in cardiac fibroblasts from streptozotocin (STZ)-treated Sprague-Dawley rats. In human cardiac fibroblasts plated on methyglyoxal-treated collagen and in cardiac fibroblasts from diabetic rats, transforming growth factor (TGF)-β2 but not TGF-β1 or TGF-β3 was increased compared with controls. Knock-down of α11 integrin and TGF-β receptors with small-interfering RNA blocked the increased expression of TGF-β2, α-smooth muscle actin (α-SMA), and α11 integrin that were induced in cells plated on methylglyoxal-treated collagen. Further, inhibition of Smad3 signalling blocked methylglyoxal-collagen up-regulation of α11 integrin and α-SMA expression. Rats with STZ-induced diabetes exhibited increased phosphorylation of Smad3 in cardiac tissues compared with control rats. CONCLUSION: Interactions between α11 integrins and the Smad-dependent TGF-β2 signalling may contribute to the formation of pro-fibrotic myofibroblasts and the development of a fibrotic interstitium in diabetic cardiomyopathy.
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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 | 0.004 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| 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) | 0.000 | 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 it