Bibliographic record
Abstract
Caveolin-1 (Cav-1) can modulate intracellular signaling pathways in airway smooth muscle (ASM) that may mediate inflammation, contraction, and/or proliferation.Previously, we observed enhanced methacholine (MCh)induced ASM contraction ex vivo and enhanced airway resistance in vivo in mice lacking Cav-1.In the present study, we investigated the possible role of Rho kinase, protein kinase C (PKC), and p42/p44 mitogen-activated protein kinase (MAPK) in the enhanced MCh-induced ASM contraction and airway resistance in Cav-1 knockout mice (Cav-1 KO).Tracheal rings from naive, 8-week-old, female Cav-1 KO and genetically matched B6129SF2/J mice were isolated and mounted on a wire myograph.Isometric contraction in response to MCh was measured in the presence or absence of selective inhibitors of Rho kinase (Y-27632, 1 mM and 10 mM), PKC (bisindolylmaleimide, 3 mM), and p42/p44 MAPK (U0126, 3 mM).The role of Rho kinase in MCh-induced airway resistance (Raw) was also investigated in vivo using a Scireq ventilator.Thirty minutes prior to measuring respiratory mechanics, Cav-1 KO and B6129SF2/J mice were exposed to aerosolized saline or Rho kinase inhibitor (5 mM Y-27632, 4 minutes).Using excised tracheal rings, maximum MCh-induced contraction was increased significantly in preparations from Cav-1 KO (8.93 6 0.77 mN) compared to B6129SF2/J mice (6.45 6 0.64 mN).Pretreatment with 10 mM Y-27632 reduced sensitivity and maximum response to MCh in both tissues and normalized the difference in contractile responses between mouse strains.Notably, whereas tracheas from Cav-1 KO exhibited concentration-dependent responses to Y-27632, maximum suppression was achieved with 1 mM of inhibitor in B6129SF2/J mice.Though we did observe a modest effect in suppressing MCh-induced contractile force with bisindolylmaleimide and U0126 treatment, the effect was of equal magnitude on Cav-1 KO and B6129SF2/J mice, suggesting that the contribution of PKC and p42/p44 MAPK to contractile responses is not changed in Cav-1 KO mice.As we previously observed in vivo, Cav-1 KO mice exhibited a significant increase in Raw and tissue resistance (G).However, consistent with our ex vivo experiments, inhaled Y-27632 both decreased Raw and G and normalized these parameters between mouse strains.Collectively, the data suggest that Cav-1 modulates the contribution of Rho kinase in MCh-mediated ASM contraction, which is a principal determinant of Raw.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.002 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.534 | 0.394 |
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; the direct Gemma label and the distilled Codex classifier agree on what is shown here.
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".