FoxO induced inhibition of secreted molecule signalling pathways: role in promoting angiostasis in the ischemic muscle
Bibliographic record
Abstract
We showed previously that FoxO1 promotes an angiostatic environment within of the vasculature of the ischemic muscle by upregulating of the extracellular matrix (ECM) protein thrombospondin‐1. Here, we aim to identify FoxO targets involved in ECM signalling. BMP and activin membrane‐bound inhibitor (BAMBI) and soluble frizzled‐related protein 1 (sFRP1) are respective inhibitors of the signals of 2 secreted molecules TGF‐β and Wnt. Primary cultures of microvascular endothelial cells (MEC) of mice having the 3 FoxO genes flanked with LoxP sites (FoxOL/L) were transduced with adeno‐Cre recombinase to delete FoxO genes. This increased BAMBI mRNA levels by 7 fold, and decreased sFRP1 expression by 2.8 fold. Conversely, over‐expression of constitutively active FoxO1 in MECs lowered BAMBI mRNA by 70% and increased sFRP1 mRNA levels by 110%. Within murine ischemic muscle (4 days post femoral artery ligation), the levels of sFRP1 were increased (p=0.055) and BAMBI expression was reduced significantly (p=0.03). Ischemia‐induced alterations in sFRP1 and BAMBI expression were abolished in mice with EC‐directed deletion of FoxO (ΔFoxO). Our data indicate that sFRP1 and BAMBI are regulated reciprocally by FoxO1. The FoxO‐dependent regulation of Wnt and TGF‐β signalling pathways may contribute to establish an angiostatic microenvironment within ischemic muscle.
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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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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 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".