Abstract P151: Short- and Long-Term Induction of Human Endothelin-1 Overexpression in Mice Up-Regulated the Expression of <i>Khdrbs3</i> in Mesenteric Arteries
Bibliographic record
Abstract
Background: Transgenic mouse with tamoxifen-inducible endothelium-restricted human ET-1 overexpression (ieET-1) exhibited blood pressure (BP) elevation three weeks (short-term) and three months after induction (long-term). Vascular injury was observed only after long-term exposure to endothelial ET-1 overexpression. It is unknown whether short or long-term exposure to ET-1 overexpression results in gene dysregulation. We aimed to identify differentially expressed (DE) microRNAs (miRs) and genes in mesenteric arteries of ieET-1 mice after short- and long-term induction of human ET-1 overexpression. Methods and Results: Ten to 12-week old male ieET-1 mice and control ieCre mice expressing a tamoxifen-inducible Cre recombinase under the control of endothelium-specific Tie2 promoter, were treated with tamoxifen (1 mg/kg/day, s.c.) for 5 days and sacrificed 16 days or 3 month later. RNA was extracted from mesenteric arteries of ieCre and ieET-1 mice and used for small and total RNA-sequencing using Illumina HiSeq-2500. EdgeR was used for differential expression analysis (false discovery rate <0.05, fold change ≤ or ≥ 1.5). No DE miRs were identified. DE genes were identified in ieET-1 compared to ieCre mice after short-term induction (mRNAs: 1 up and 6 down; non-coding [nc]RNAs: 3 up) and after long-term induction (mRNA: 1 up). Khdrbs3 (KH domain containing, RNA binding, signal transduction associated 3), which was up-regulated after both short- and long-term exposure to endothelial ET-1 overexpression, was validated by reverse transcription-quantitative PCR (RT-qPCR). We demonstrated a correlation between RNA-sequencing and RT-qPCR data for short- and long-term groups (r=0.8, P <0.0005). The mRNA expression of Khdrbs3 was 2 times more in fibroblasts than in smooth muscle cells and endothelial cells (2.37±0.28 vs. 1.11±0.17 and 1.12±0.12, P <0.01). Conclusions: The results showed that short- and long-term exposure to endothelial ET-1 overexpression up-regulated Khdrbs3 in mesenteric arteries. In vitro study revealed that this gene was expressed to a greater level in fibroblasts than other vascular cells. However, the role of Khdrbs3 in ET-1-induced vascular injury remains to be determined.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.005 | 0.001 |
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 source (direct Gemma or distilled Codex), 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".