Angiotensin-(1–7) activates growth-stimulatory pathways in human mesangial cells
Bibliographic record
Abstract
Angiotensin-(1-7) [Ang-(1-7)] is generated in part via ACE2-dependent degradation of angiotensin II (ANG II). In proximal tubular cells, Ang-(1-7) inhibits ANG II-stimulated phosphorylation of the mitogen-activated protein kinases (MAPKs) p38, extracellular signal-related kinase (ERK1/ERK2), and c-jun N-terminal kinase (JNK), suggesting that Ang-(1-7) protects against ANG II-mediated tubulointerstitial injury. We determined the effect of Ang-(1-7) on signaling and growth responses in cultured human mesangial cells. Ang-(1-7) increased phosphorylation of p38, ERK1/ERK2, and JNK MAPKs, which was blocked by the Ang-(1-7) antagonist A-779. Neither the AT(1) receptor antagonist losartan, nor the AT(2) antagonist PD123319 affected specific binding of [(125)I]Ang-(1-7) or Ang-(1-7)-stimulated p38 phosphorylation. Ang-(1-7) increased cell arachidonic acid release, an effect blocked by A-779. The p38 MAPK antagonist SB202190 completely prevented Ang-(1-7)-stimulated release of arachidonic acid, whereas inhibitors of ERK or JNK had no effect. Ang-(1-7) significantly enhanced DNA synthesis and increased production of transforming growth factor-beta1 (TGF-beta1), fibronectin, and collagen IV. Both A-779 and SB202190 blocked the Ang-(1-7)-stimulated increases in TGF-beta1, fibronectin, and collagen IV. These data indicate that Ang-(1-7) activates MAPK phosphorylation via binding to a specific receptor in human mesangial cells. Stimulation of p38 MAPK phosphorylation by Ang-(1-7) leads to release of arachidonic acid and production of TGF-beta1 and extracellular matrix proteins. We conclude that Ang-(1-7) exerts growth-stimulatory effects in human mesangial cells.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.002 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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".