Bibliographic record
Abstract
Migration of activated fibroblasts within the alveolar compartment, their transition to myofibroblasts, and extensive secretion of extracellular matrix constituents are indicative for active fibrogenesis. By using a three dimensional collagen-based invasion assay we generated a transcriptome-wide signature of invading fibroblasts by microarray analysis. Within this signature the secreted frizzled-related protein (SFRP1), a Wnt signaling pathway inhibitor, was identified as a negative regulator of fibroblast invasion. Treatment with the pro-fibrotic master regulator TGFb1 augmented the fibroblasts’ invasive capacity but further suppressed the expression of SFRP1. However, in a proteomic profiling of the matrisome of fibrotic mouse lungs during a time course, SFRP1 expression was found to be highly upregulated in the total tissue homogenates of fibrotic lungs. This increased expression of SFRP1 in fibrotic lungs was further confirmed on transcript and protein levels, as well as by immunohistochemical stainings. In-depth immunohistochemical analyses of fibrotic mouse lungs revealed high levels of SFRP1 expression in E-Cadherin and partially in Desmin positive cells, but not in aSMA positive myofibroblasts. In human IPF sections a strong expression of SFRP1 was discovered in basal cells of the bronchial epithelium, which may indicate a role of SFRP1 in tissue remodeling and regeneration. In-vitro, expression of SFRP1 was found in primary human fibroblasts, human bronchial epithelial cells (16-HBE) and primary human basal cells. In conclusion, we argue for a dual role of SFRP1 in lung fibrosis showing low SFRP1 expression in invading fibroblasts and myofibroblasts, and a high SFRP1 expression in the remodeled epithelial compartment.
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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) | 0.000 | 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 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".