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Potential role of ATF2 and MEF2C in shear stress‐mediated VEGF production

2009· article· en· W118913947 on OpenAlexafffund
Eric Gee, Tomasz Fudalewski, Tara L. Haas

Bibliographic record

VenueThe FASEB Journal · 2009
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicAngiogenesis and VEGF in Cancer
Canadian institutionsYork University
FundersNatural Sciences and Engineering Research Council of Canada
KeywordsMEF2Cp38 mitogen-activated protein kinasesShear stressWestern blotCREBPhosphorylationInternal medicineEndocrinologyBiologyChemistryCell biologyMedicineMaterials scienceTranscription factorMAPK/ERK pathwayBiochemistry

Abstract

fetched live from OpenAlex

Increased capillary shear stress in skeletal muscle causes a form of angiogenesis termed luminal splitting. An increased number of capillaries are observed at 7 days of chronic shear stress that is reliant on p38 signaling. Others have shown that VEGF is essential for luminal splitting. We hypothesize that VEGF production is p38 dependent and is increased by p38 dependent transcription factors Creb, ATF2 and MEF2C in response to shear stress. Male Sprague‐Dawley rats were administered prazosin (50 mg/L drinking water) to increase shear stress, and the extensor digitorum longus was extracted at 1, 2, 4 or 7 days. By Western blot, p38 was activated only at 2 days. Skeletal muscle endothelial cells were sheared (12 dynes/cm 2 ) with or without 10 μM SB203580 (p38 inhibitor), then lysed and analyzed by RT‐PCR or Western blot. In vitro, shear stress induced VEGF mRNA and protein elevation at 2 and 6 hours, respectively. These increases were abolished by SB203580. Shear stress increased both ATF2 phosphorylation and MEF2C production at 2 hours, which were abrogated by SB203580. Creb phosphorylation was unchanged by shear stress. Our data show that shear stress‐mediated p38 activation is required for VEGF production. ATF2 phosphorylation and MEF2C production are increased by shear stress, but further investigation is necessary to determine if they mediate p38‐induced VEGF production. Supported by HSF and NSERC. Grant Funding Source The Heart and Stroke Foundation

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 machine prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.007

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.000

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.

Opus teacher head0.006
GPT teacher head0.226
Teacher spread0.221 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

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".

Quick stats

Citations0
Published2009
Admission routes2
Has abstractyes

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