Role of Growth factor receptor transactivation in high glucose‐induced increased levels of Gq/11α and signaling in vascular smooth muscle cells
Bibliographic record
Abstract
We have recently shown that high glucose (HG) increased the expression of Gq/11α, PLCβ and mediated signaling in A10 vascular smooth muscle cells (VSMC). Since HG has been shown to increase growth factor receptor (GFR) activation, we investigated the role of epidermal growth factor receptor (EGF‐R) and platelet‐derived growth factor receptor (PDGF‐R) transactivation in HG‐induced enhanced expression of Gq/11α and PLCβ. Pre‐treatment of A10 VSMC with HG (26 mM) for 3 days, increased the levels of Gqα, G11α, PLCβ‐1 and PLCβ‐2 proteins as determined by Western blotting which were restored to control levels by AG1478, an inhibitor of EGF‐R, AG1295, an inhibitor of PDGF‐R and PP2, an inhibitor of c‐Src but not by PP3. In addition, endothelin‐1 (ET‐1)‐stimulated production of IP 3 that was enhanced by HG was also restored towards control levels by AG1478, AG1295 and PP2. HG also increased the phosphorylation of EGF‐R and PDGF‐R which was abolished by AG1478, AG1295 and PP2. Furthermore, HG‐induced enhanced levels of Gqα, G11α and PLCβ were also attenuated by inhibition of MAP Kinase, PI3‐Kinase and c‐Src. In addition, GFR inhibitors also attenuated HG‐induced enhanced phosphorylation of ERK1/2 and AKT. These results suggest that c‐Src‐induced transactivation of growth factor receptor contributes to the high glucose‐induced enhanced expression of Gq/11α/PLC and ‐mediated cell signaling through MAPK/PI3K pathway. This work was supported by Canadian Institutes of Health Research grant
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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) | 0.000 | 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 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".