Cystathionine gamma-lyase deficiency and overproliferation of smooth muscle cells
Why this work is in the frame
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Bibliographic record
Abstract
AIMS: Cystathionine gamma-lyase (CSE)-derived H2S plays an important role in regulating cell growth. Lack of CSE expression results in development of hypertension. The current study compared proliferation of smooth muscle cells derived from CSE gene knockout mice (SMCs-KO) with that of wild-type mice (SMCs-WT). METHODS AND RESULTS: Cell proliferation was assessed by bromodeoxyuridine incorporation. Gene expression was analysed by western blotting, real-time PCR, and microarray analysis. Enhanced cell proliferation was detected in SMCs-KO and in the media of the aorta from CSE KO mice. SMCs-KO underwent significantly more apoptosis than SMCs-WT when treated with exogenous H2S (100 microM). CSE KO mice showed much lower level of phosphorylated extracellular signal-regulated kinase (ERK1/2) in mesentery arteries compared with those of WT mice, and exogenous H2S induced more phosphorylation of ERK1/2 in SMCs-KO compared with that in SMCs-WT. Decreased p21(Cip/WAF-1) but increased cyclin D1 expression was observed in isolated SMCs and vascular tissues from CSE KO mice, and exogenous H2S caused more increase in p21(Cip/WAF-1) expression and more decrease in cyclin D1 expression in SMCs-KO than in SMCs-WT. The transcriptional expression of calcitonin receptor-like, intergrin beta 1, and heparin-binding epidermal growth factor-like growth factor was also significantly increased in the aorta of CSE KO mice. CONCLUSION: SMCs-KO display an increased proliferation rate in vitro and in vivo, and these cells are more susceptible to apoptosis induced by exogenous H2S at physiologically relevant concentrations. These cellular effects of H2S are mediated by phosphorylation of ERK1/2 and altered expression of cyclin D1 and p21(Cip/WAF-1).
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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 | 0.002 | 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) | 0.000 | 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 it