Mmp12 Is Upregulated by in utero Second-Hand Smoke Exposures and Is a Key Factor Contributing to Aggravated Lung Responses in Adult Emphysema, Asthma, and Lung Cancer Mouse Models
Bibliographic record
Abstract
Matrix metalloproteinase-12 (Mmp12) is upregulated by cigarette smoke (CS) and plays a critical role in extracellular matrix remodeling, a key mechanism involved in physiological repair processes, and in the pathogenesis of emphysema, asthma, and lung cancer. While cigarette smoking is associated with the development of chronic obstructive pulmonary diseases (COPD) and lung cancer,in uteroexposures to CS and second-hand smoke (SHS) are associated with asthma development in the offspring. SHS is an indoor air pollutant that causes known adverse health effects; however, the mechanisms by whichin uteroSHS exposures predispose to adult lung diseases, including COPD, asthma, and lung cancer, are poorly understood. In this study, we tested the hypothesis thatin uteroSHS exposure aggravates adult-induced emphysema, asthma, and lung cancer. Methods:Pregnant BALB/c mice were exposed from gestational days 6–19 to either 3 or 10mg/m3of SHS or filtered air. At 10, 11, 16, or 17weeks of age, female offspring were treated with either saline for controls, elastase to induce emphysema, house-dust mite (HDM) to initiate asthma, or urethane to promote lung cancer. At sacrifice, specific disease-related lung responses including lung function, inflammation, gene, and protein expression were assessed. Results:In the elastase-induced emphysema model,in uteroSHS-exposed mice had significantly enlarged airspaces and up-regulated expression ofMmp12(10.3-fold compared to air-elastase controls). In the HDM-induced asthma model,in uteroexposures to SHS produced eosinophilic lung inflammation and potentiatedMmp12gene expression (5.7-fold compared to air-HDM controls). In the lung cancer model,in uteroexposures to SHS significantly increased the number of intrapulmonary metastases at 58weeks of age and up-regulatedMmp12(9.3-fold compared to air-urethane controls). In all lung disease models,Mmp12upregulation was supported at the protein level. Conclusion:Our findings revealed thatin uteroSHS exposures exacerbate lung responses to adult-induced emphysema, asthma, and lung cancer. Our data show that MMP12 is up-regulated at the gene and protein levels in three distinct adult lung disease models followingin uteroSHS exposures, suggesting that MMP12 is central toin uteroSHS-aggravated lung responses.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| 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) | 0.002 | 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".