Shear stress activates extracellular signal‐regulated kinase 1/2 <i>via</i> the angiotensin II type 1 receptor
Bibliographic record
Abstract
Mechanical factors such as strain, pressure, and shear stress are key regulators of cell function, but the molecular mechanisms underlying the detection and responses to such stimuli are poorly understood. Whether the angiotensin II (AngII) AT1 receptor (AT1R) transduces shear stress in endothelial cells (ECs) is unknown. We exposed human umbilical cord endothelial cells (HUVECs) to a shear stress of 0 (control) or 15 dyn/cm(2) for 5 or 10 min. The colocalization of AT1R with caveolin-1 (Cav1), endosomal markers Rab5, EEA1, and Rab7, and lysosomal marker Lamp-1 increased in shear stimulated cells, detected by immunocytochemistry. Shear stress reduced labeling of wild-type mouse ECs (18±3% of unsheared control, P<0.01) but not Cav1(-/-) ECs (90±10%) with fluorescent AngII, confirming that internalization of AT1R requires Cav1. Shear stress activated ERK1/2 2-fold (P<0.01), which was prevented by the AT1R blocker losartan. NADPH oxidase inhibition with apocynin prevented both the colocalization of AT1R with Cav1 and the induction of ERK1/2 by shear stress. Moreover, shear-dependent ERK1/2 activation was minimal in CHO cells expressing an AT1Ra mutant that does not internalize, compared with cells expressing wild-type AT1Ra (P<0.05). Hence, AT1R may be an important transducer of shear stress-dependent activation of ERK1/2.
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How this classification was reachedexpand
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 | 0.001 | 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 | 0.001 | 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) | 0.001 | 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 teacher head, 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".