Epigenetic modification of intestinal smooth muscle cell phenotype during proliferation
Bibliographic record
Abstract
Inflammation causes proliferation of intestinal smooth muscle cells (ISMC), contributing to a thickened intestinal wall and to stricture formation in Crohn's disease. Proliferation of ISMC in vitro and in vivo caused decreased expression of marker proteins, but the underlying cause is unclear. Since epigenetic change is important in other systems, we used immunocytochemistry, immunoblotting, and quantitative PCR to examine epigenetic modification in cell lines from rat colon at low passage or after extended growth to evaluate phenotype. Exposure to the histone deacetylase (HDAC) inhibitor trichostatin A or the DNA methyltransferase inhibitor 5-azacytidine reversed the characteristic loss of phenotypic markers among high-passage cell lines of ISMC. Expression of smooth muscle actin and smooth muscle protein 22, as well as functional expression of the neurotrophin glial cell line-derived neurotrophic factor, was markedly increased. Increased expression of muscarinic receptor 3 and myosin light chain kinase was correlated with an upregulated response to cholinergic stimulation. In human ISMC (hISMC) lines from the terminal ileum, phenotype was similarly affected by extended proliferation. However, in hISMC from resected Crohn's strictures, we observed a significantly reduced contractile phenotype compared with patient-matched intrinsic controls that was associated with increased patient-specific expression of DNA methyltransferase 1, HDAC2, and HDAC5. Therefore, protracted growth causes epigenetic alterations that account for an altered phenotype of ISMC. A similar process may promote stricture formation in Crohn's disease, where the potential for halting progression, or even reversal, of disease through control of phenotypic modulation may become a novel treatment option.
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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) | 0.001 | 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".