Mechanical Strain-Induced RhoA Activation Requires NADPH Oxidase-Mediated ROS Generation in Caveolae
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Bibliographic record
Abstract
Increased intraglomerular pressure leads to kidney fibrosis, and can be modeled by exposing glomerular mesangial cells (MC) to mechanical strain. We previously showed that RhoA mediates strain-induced matrix production. Here we investigate whether reactive oxygen species (ROS) are required for RhoA activation. Maximal RhoA activation (1 min) was inhibited by ROS scavenge or NADPH oxidase inhibition. Strain activated NADPH oxidase, with Rac1, p47(phox), and p67(phox) membrane translocation, and Rac1 activation, observed within 30 sec. Epidermal growth factor receptor (EGFR) inhibition blocked RhoA and Rac1 activation, p67(phox) membrane translocation, and ROS generation. However, EGFR activation was unaffected by ROS inhibitors, placing it upstream of ROS generation. We previously showed, using chemical disruption, that caveolae mediate strain-induced EGFR and RhoA activation. In MC from caveolin-1 knockout mice, which lack caveolae, RhoA and Rac1 activation, p67(phox) membrane translocation, and ROS generation were absent. These were rescued by caveolin-1 re-expression. ROS generation, Rac1 activation, and p67(phox) membrane translocation were also prevented by Src inhibition. They were absent in MC stably infected with caveolin-1 Y14A, a mutant resistant to Src phosphorylation. In MC, caveolae are thus important mediators of strain-induced ROS generation through NADPH oxidase, mediating a signaling cascade which results in RhoA activation.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 it