Abstract 485: Transglutaminase 2 is a Regulator of Angiotensin II-induced ERK1/2 Activation in Vascular Smooth Muscle Cells.
Bibliographic record
Abstract
Background: In essential hypertension, angiotensin (Ang) II induces arterial remodeling that is dependent on the activation of ERK1/2 pathway in vascular smooth muscle cells (VSMC). Arterial remodeling is also dependent on transglutaminase 2 (TG2), a protein with an emerging role in vascular pathophysiology. Beside its effect on extracellular matrix, TG2 is a multifunctional protein with GTPase activity and as such, could potentially be a signaling molecule. We hypothesized that TG2 mediates Ang II-induced ERK1/2 activation in VSMC during arterial remodeling. Methods and Results: To determine the role of TG2 in Ang II type 1 receptor (AT 1 R) signaling, His 6 tagged-TG2 was overexpressed in the human embryonic kidney (HEK) 293 cell line stably overexpressing HA tagged-AT 1 R. Protein and phosphorylation levels were determined by Western blot. When stimulated for 2-60 min, TG2 overexpression potentiated 100 nM Ang II-induced ERK1/2 phosphorylation compared to control cells overexpressing green fluorescent protein (GFP, P <0.05, n=4). Maximal potentiation was observed after 2 min of stimulation at which time TG2 transfected cells showed an increase of 64±31% compared to GFP transfected cells. The role of TG2 in Ang II-induced phosphorylation of ERK1/2 was studied by TG2 siRNA knockdown in mouse vascular smooth muscle cell line (MOVAS). TG2 siRNA decreased TG2 expression by 83±5% compared to cells treated with control siRNA (n=4). Transfection of TG2 siRNA did not significantly change cell viability when compared to ctrl siRNA (n=3). Ten min stimulation with 1 and 100 nM Ang II increased ERK1/2 phosphorylation by 38±18% and 60±29%, respectively, and this was prevented by TG2 knockdown ( P <0.01). Using western blots, HA-AT 1 R dimer/monomer ratio was increased by co-expression of His 6 -TG2 compared to HA-AT1R expressed alone. Conclusion: These results suggest that TG2 mediates ERK1/2 activation by Ang II through a mechanism involving TG2-induced AT 1 R dimerization. Overall, our results demonstrate that TG2 is involved in the activation of ERK1/2 in response to Ang II and could participate in arterial remodeling induced by Ang II.
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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".