STIM‐1 and ORAI‐1 channel mediate angiotensin‐II‐induced expression of Egr‐1 in vascular smooth muscle cells
Bibliographic record
Abstract
An upregulation of Egr‐1 expression has been reported in models of atherosclerosis and intimal hyperplasia and, 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 key vasoactive peptide that has been implicated in the pathogenesis of vascular diseases. Ang‐II elevates intracellular Ca 2+ through activation of the store‐operated calcium entry (SOCE) involving an inositol‐3‐phosphate receptor (IP3R)‐coupled depletion of endoplasmic reticular Ca 2+ and a subsequent activation of the stromal interaction molecule 1 (STIM‐1)/Orai‐1 complex. However, the involvement of IP3R/STIM‐1/Orai‐1‐Ca 2+ ‐dependent signaling in Egr‐1 expression in VSMC remains unexplored. Therefore, in the present studies, we have examined the role of Ca 2+ signaling in Ang‐II‐induced Egr‐1 expression in VSMC and investigated the contribution of STIM‐1 or Orai‐1 in mediating this response. 2‐aminoethoxydiphenyl borate (2‐APB), a dual non‐competitive antagonist of IP3R and inhibitor of SOCE, decreased Ang‐II‐induced Ca 2+ release and attenuated Ang‐II‐induced enhanced expression of Egr‐1 protein and mRNA levels. Egr‐1 upregulation was also suppressed following blockade of calmodulin and CaMKII. Furthermore, RNA interference‐mediated depletion of STIM‐1 or Orai‐1 attenuated Ang‐II‐induced Egr‐1 expression as well as Ang‐II‐induced phosphorylation of ERK1/2 and CREB. In addition, siRNA‐induced silencing of CREB resulted in a reduction in the expression of Egr‐1 stimulated by Ang‐II. In summary, our data demonstrate that Ang‐II‐induced Egr‐1 expression is mediated by STIM‐1/Orai‐1/Ca 2+ ‐dependent signaling pathways in A‐10 VSMC.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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) | 0.001 | 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".