A potential role for Gremlin 1 in pulmonary postnatal maturation and neonatal hypoxia-induced pulmonary hypertension
Bibliographic record
Abstract
During early postnatal life, the lung undergoes profound adaptive processes as a result of taking on the function of gas exchange and neonates may be particularly vulnerable to developing pulmonary hypertension. The bone morphogenetic protein (BMP) antagonist, Gremlin 1 (GREM1) has been recently suggested to contribute to the development of pulmonary arterial hypertension (Cahill E. et al., Circulation 2012; 125: 920-30). The aim of this study was to analyze the role of GREM1 during pulmonary postnatal development and upon hypoxic challenge in the neonatal period. C57/Bl6 newborn mice were randomly placed into normoxic (21% O2) or normobaric hypoxic (13% O2) chambers for 2 weeks. Adult mice (10 weeks-old) were used for comparison. Vascular reactivity was assessed using intrapulmonary arteries mounted into isometric wire myographs and lung mRNA levels were analysed by real time PCR. Lung mRNA levels of the BMP receptor BMPR2 increased 1.5-fold with postnatal age alongside a 4-fold decrease in the BMP antagonist GREM1. Exposure to chronic hypoxia during the first 2 weeks of life decreased the expression levels of BMPRII by 1.4-fold and upregulated GREM1 by 2.3-fold. In addition, exposure of 2-weeks-old PA to GREM1 (100ng/mL) for 20 hours significantly increased the contractile responses to high potassium and to the thromboxane A2 mimetic U46619. These findings suggest that a maturational decrease in the expression of the BMP antagonist GREM1 occurs during postnatal development and may contribute to the regulation of pulmonary vascular tone. Supported by Spanish MINECO (2011-28150) and ISCIII (CP12/03304).
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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 | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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 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".