Vitamin D Receptor Deletion Leads to an Asthma Phenotype
Bibliographic record
Abstract
Background Despite strong epidemiological association between the perinatal vitamin D (VD) deficiency and childhood asthma, the mechanistic link between the two is not established. We aimed to determine the effect of VD receptor deletion on the key markers of lung maturation. Methods The lungs of wild type and VD receptor null mutant mice (C57BL6) were examined at 2 and 7 weeks postnatally for morphometry and markers of lung maturation by RT-PCR, Western blotting, and immunohistochemistry (IHC). Using the Affymetrix Mouse Genome 430 2.0 array, the transcriptional profile of the lungs from the two groups at 7 weeks of age was also examined. Results Both by Western analysis and IHC, there was down-regulation of the intermediates for PTHrP/PPARγ signaling, a key signaling pathway for lung maturation. In contrast, there was up-regulation of Wnt signaling, a key pathway in the pathogenesis of asthma. Self-Organizing Map cluster analysis corroborated these data by showing up-regulation of the Wnt signaling pathway, and down-regulation of the PTHrP/PPARγ signaling pathway in VD receptor null mice compared to WT mice. Conclusions Altered VD signaling leads to down-regulation of homeostatic PTHrP/PPARγ signaling, and up-regulation of Wnt signaling, predisposing to a myogenic pulmonary phenotype that is consistent with the propensity to asthma in VD deficiency (Grants: HL75405, HD51857, HD58948).
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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 | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 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".