Involvement of Stromal Interaction Molecule‐1 in Angiotensin‐II‐Induced Expression of The Early Growth Response Protein‐1 in Vascular Smooth Muscle Cells
Bibliographic record
Abstract
The early growth response protein 1 (Egr‐1) is a zinc finger transcription factor that has been suggested to regulate the expression of genes linked with inflammation and cell cycle regulation. An up‐regulation of Egr‐1 expression has been reported in models of atherosclerosis and intimal hyperplasia. Various vasoactive peptides and growth promoting stimuli have been shown to induce the expression of Egr‐1 in vascular smooth muscle cells (VSMC). Angiotensin‐II (Ang‐II) is a critical vasoactive peptide implicated in the pathogenesis of vascular diseases. Ang‐II elevates the intracellular level of Ca 2+ through activation of store‐operated Ca 2+ entry involving inositol‐3‐phosphate receptor (IP3R)‐coupled depletion of endoplasmic reticular Ca 2+ and stromal interaction molecule 1 (STIM‐1). However, an involvement of IP3R/STIM‐1‐induced Ca 2+ signaling pathway in Ang‐II‐induced Egr‐1 expression remains unexplored. Therefore in the present studies we have examined the role of Ang‐II‐induced Ca 2+ release in Egr‐1 expression in VSMC and investigated the contribution of STIM‐1 in this process. Ca 2+ chelation with BAPTA‐AM as well as pharmacological blockade of IP3R with 2‐aminoethoxydiphenyl borate (2‐APB) reduced Ang‐II‐induced Ca 2+ release in VSMC loaded with Fura‐2 AM. Consistent with this, both BAPTA‐AM and 2‐APB attenuated Ang‐II‐induced enhanced expression of Egr‐1 protein levels. In addition, pharmacological blockade of both the epidermal growth factor receptor and the insulin‐like growth factor‐1 receptor attenuated Ca 2+ release and inhibited the Egr‐1 up‐regulation induced by Ang‐II. Furthermore, silencing of STIM‐1 via RNA interference significantly abrogated STIM‐1 protein and mRNA expression and resulted in an attenuation of Ang‐II‐induced Egr‐1 expression as well as ERK1/2 phosphorylation. In summary, our data demonstrate that Ang‐II‐induced Egr‐1 expression is mediated by STIM‐1 and Ca 2+ release in A‐10 VSMC and suggest an implication of STIM‐1 in the pathogenesis of vascular proliferative diseases. Support or Funding Information Supported by a grant from the Canadian Institutes of Health Research
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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 | 0.002 | 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 | 0.001 |
| 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".