Abstract 19233: C-myb Regulates Microrna143 and Microrna145 Gene Expression in Embryonic and Adult Vascular Smooth Muscle Cells
Bibliographic record
Abstract
Background: MicroRNAs (miR) are small non-coding RNAs. The bicistronic miR-143/145 gene determines cell fate of cardiomyocytes, vascular smooth muscle cells (VSMC) and endothelial cells. The regulation of miR-143/145 remains unclear. Transcription factor c-Myb controls proliferation and differentiation of hematopoiesis progenitors and VSMC. Hypothesis: c-Myb regulates miR-143/145 expression in VSMC proliferation and differentiation. Methods & Results: Flow cytometry of d3.75 mouse embryoid bodies (EBs) was used to isolate SMC progenitors with surface markers VEGFR2 (V) and PDGFRα (P). In c-myb knockout EB, V + /P - and V-/P+ progenitor cells had low expression of miR-143/145 suggesting a role for c-Myb in their regulation. Primary carotid VSMC isolated from mice with diminished expression of c-Myb (LoxP) treated with TGFβ have reduced expression of miR-143 and miR-145. Sequence alignment identified c-Myb-binding sites (MBS) in the promoter of the miR-143/145 gene. ChIP assays in EBs and adult VSMC revealed c-Myb binding to MBS. Using site-directed mutagenesis in a promoter-reporter construct, we identified MBS mediate transcriptional regulation of miR-143/145 in VSMC. Immunoblots were used to test whether c-Myb regulated a known target of miR-143, the ETS domain-containing protein-1 (Elk-1). Increased levels of c-Myb inversely correlated with Elk-1, suggesting c-Myb represses Elk-1. This effect was abrogated by miR-143 antagomir, and enhanced by miR-143 mimic. Conclusion: c-Myb regulates miR-143/145 expression in differentiating embryonic SMC progenitors and TGFβ-stimulated adult VSMC via MBS in the miR-143/145 promoter.
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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) | 0.000 | 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) | 0.007 | 0.002 |
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".