Tripeptide IRW increases epithelial cadherin (E-cadherin) level via angiotensin converting enzyme 2 (ACE2) axis
Bibliographic record
Abstract
The tripeptide IRW has been shown to upregulate E-cadherin expression in the aortas of spontaneously hypertensive rats (SHRs). E-cadherin, a transmembrane glycoprotein, plays a key role in cell–cell adhesion, migration, proliferation, survival, and differentiation. Given the mechanistic function of angiotensin-converting enzyme 2 (ACE2) in IRW’s blood pressure regulation, this study aimed to explore the role of ACE2 axis in the regulation of E-cadherin by IRW. IRW increased E-cadherin expression, reduced zinc finger protein SNAI1 (Snail1), and intracellular Ca 2+ concentration in both A7r5 rat aortic vascular small muscle cells and the aorta of SHRs. However, calcium release-activated calcium modulator 1 (Orai 1) expression was reduced only in A7r5 cells, but not in SHRs. Co-treatment of IRW with angiotensin II (Ang II), ACE2 knockdown or Mas receptor (MasR) antagonist abolished the ability of IRW to increase E-cadherin expression in A7r5 cells. Tamoxifen increased E-cadherin expression in A7r5 cells without affecting ACE2 levels. Our findings suggest that the ACE2 axis and Orai1/Ca2 + pathway play a key role in the regulation of E-cadherin by IRW. • Tripeptide IRW upregulated E-cadherin in vascular smooth muscle cells and SHR aortas. • IRW suppresses cell migration, reducing Snail1 expression and intracellular Ca²⁺ levels. • The decrease of Ca²⁺ in vascular smooth muscle cells is related to Orai1 reduction. • ACE2/Ang-(1–7)/Mas axis is involved in IRW-induced E-cadherin upregulation. • IRW shows protective effects by reducing vascular remodeling, proliferation, and migration.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 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".