Transforming growth factor β-induced peritoneal fibrosis is mouse strain dependent*
Bibliographic record
Abstract
BACKGROUND: Encapsulating peritoneal sclerosis (EPS) is a rare but devastating complication of peritoneal dialysis. The etiology is unclear, but genetic predisposition may be a contributing factor. We used adenovirus-mediated gene transfer of transforming growth factor (TGF) β1 to the peritoneum in four genetically distinct laboratory mouse strains to assess differences in fibrogenic response. METHODS: Mice from four genetic backgrounds (C57BL/6J, DBA/2J, C3H/HeJ and SJL/J) received an intraperitoneal injection of an adenovirus expressing TGFβ1 (AdTGFβ1) or control adenovirus (AdDL) and were assessed 4 and 10 days after infection. Submesothelial thickening, angiogenesis and gene expression were quantified from peritoneal tissue. Protein was extracted from omental tissue and assessed for collagen, E-cadherin and TGFβ signaling pathway proteins. RESULTS: There was a graded response among the mouse strains to the peritoneal overexpression of TGFβ1. TGFβ1 induced a significant fibrogenic response in the C57BL/6J mice, whereas the SJL/J mice were resistant. The DBA/2J and the C3H/HeJ mice had intermediate responses. A similar graded response was seen in collagen protein levels in the omental tissue and in fibrosis-associated gene expression. TGFβ type 1 receptor and SMAD signaling pathways appeared to be intact in all the mouse strains. CONCLUSIONS: There were significant differences in mouse strain susceptibility to peritoneal fibrosis, suggesting that genetic factors may play a role in the development of peritoneal fibrosis and possibly EPS. As early TGFβ1 signaling mechanisms appear to be intact, we hypothesize that fibrosis resistance in the SJL/J mice lies further down the wound-healing cascade or in an alternate, non-SMAD pathway.
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How this classification was reachedexpand
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 | 0.000 | 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 teacher head, 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".