miR204/RUNX2 axis regulates HIF‐1α activation in pulmonary arterial hypertension
Bibliographic record
Abstract
Pulmonary arterial hypertension (PAH) is characterized by proliferation and apoptosis resistance of pulmonary artery smooth muscle cells (PASMC). This phenotype is sustained by an elusive HIF‐1α activation RUNX2 activates HIF‐1α in vascular diseases, and is controlled by miR‐204 that is decrease in PAH. We hypothesized that miR‐204 downregulation triggers RUNX2‐dependent activation of HIF‐1 contributing to PAH. HIF‐1α and RUNX2 activation are increased in humans and rats distal PA and PAH‐PASMC vs control. In PAH‐PASMC, RUNX2 downregulation resulted in HIF‐1α inhibition (immunoblot, IF; p<0.05) decreasing proliferation (p<0.05) and resistance to apoptosis (p<0.05); while RUNX2 upregulation in control PASMC has the opposite effects. As RUNX2 is one of the predicted targets of miR‐204 its upregulation in PAH‐PASMC could be explained by the miR‐204 downregulation seen in PAH. Thus miR‐204 supplementation (mimic) in PAH‐PASMC decreases RUNX2 and HIF‐1α activation (Western blot; p<0.05), while miR‐204 downregultion in control PASMC increases RUNX2 and HIF‐1. In vivo, siRUNX2 nebulization or miR‐204 nebulization in SUGEN‐induced PAH rats reverses PAH. We demonstrated the implication of miR‐204/RUNX2 axis in HIF‐1 activation in PAH.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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 source (direct Gemma or distilled Codex), 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".