Modulation of reactive oxygen species and MMP9 by Rac1 prevents asbestos‐induced pulmonary fibrosis
Bibliographic record
Abstract
The release of reactive oxygen species (ROS) and cytokines by alveolar macrophages has been demonstrated in asbestos‐induced pulmonary fibrosis, but the mechanism linking alveolar macrophages to the pathogenesis is not known. The GTPase Rac1 is a second messenger that plays an important role in host defense. In this study, we demonstrate that Rac1 null mice are protected from asbestos‐induced pulmonary fibrosis. We hypothesized that Rac1 induced pulmonary fibrosis via generation of ROS. Asbestos increased ROS in a Rac1‐dependent manner with ROS being significantly greater in wild type (WT) mice compared to Rac1 null mice. Extracellular matrix degradation was dependent on Rac1 activity and ROS. Expression of the macrophage specific metalloproteinase, MMP9, was significantly less in WT cells compared to Rac1 null cells. In addition, Rac1 null cells exhibited enhanced gene expression driven by AP1, an important transcription factor in MMP9 expression. Over expression of catalase decreased ROS generation and increased MMP9 expression in vitro. Importantly, administration of catalase to WT mice attenuated the development of fibrosis in vivo . For the first time, these results demonstrate that Rac1 plays a crucial role in asbestos‐induced pulmonary fibrosis. Moreover, it suggests that a simple intervention may be useful to prevent progression of the disease. This work was supported by NIH grant ES‐015981.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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) | 0.001 | 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 | 0.000 |
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".