High glucose-enhanced activation of mesangial cell p38 MAPK by ET-1, ANG II, and platelet-derived growth factor
Bibliographic record
Abstract
Mitogen-activated protein kinase (MAPK) p38 is activated in response to stress stimuli and growth factors relevant to the pathogenesis of diabetic nephropathy. We postulated that mesangial cells exposed to high glucose and to endothelin-1 (ET-1), angiotensin II (ANG II), and platelet-derived growth factor (PDGF) demonstrate enhanced p38 activity and subsequent activation of the cAMP responsive element binding (CREB) transcription factor. Primary rat mesangial cells exposed to 5.6 (NG) or 30 mM glucose (HG) or NG plus 24.4 mM sorbitol (osmotic control) for < or = 4 days were acutely stimulated with ET-1, ANG II, or PDGF. After 3 days of HG, p38 phosphorylation and kinase activity increased twofold (P < 0.05 vs. NG, n = 5). No change in p38 activity was observed with sorbitol. In HG, activation of p38 by ET-1, ANG II, or PDGF was enhanced compared with NG and was protein kinase C (PKC) independent. In HG, CREB phosphorylation in response to ET-1, ANG II, and PDGF stimulation was enhanced compared with NG and was abolished by p38 inhibition with SB202190. To conclude, in HG, mesangial cell p38 is activated, which in turn stimulates CREB phosphorylation. Furthermore, in HG, mesangial cell p38 responsiveness to ET-1, ANG II, and PDGF and consequent CREB phosphorylation are enhanced through a PKC-independent pathway, which may contribute to the pathogenesis of diabetic nephropathy.
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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 | 0.000 | 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 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".