Skin Progenitor Cells Contribute to Bleomycin‐Induced Skin Fibrosis
Why this work is in the frame
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Bibliographic record
Abstract
OBJECTIVE: The origin of the cells that contribute to skin fibrosis is unclear. We undertook the present study to assess the contribution of Sox2-expressing skin progenitor cells to bleomycin-induced scleroderma. METHODS: Scleroderma was induced, by bleomycin administration, in wild-type mice and in mice in which CCN2 was deleted from Sox2-expressing cells. Lineage tracing analysis was performed to assess whether cells expressing Sox2 are recruited to fibrotic lesions in response to bleomycin-induced scleroderma. RESULTS: In response to bleomycin, Sox2-positive/α-smooth muscle actin-positive cells were recruited to fibrotic tissue. CCN2-conditional knockout mice in which CCN2 was deleted from Sox2-expressing cells exhibited resistance to bleomycin-induced skin fibrosis. Collectively, these results indicate that CCN2 is required for the recruitment of progenitor cells and that CCN2-expressing progenitor cells are essential for bleomycin-induced skin fibrosis. Lineage tracing analysis using mice in which a tamoxifen-dependent Cre recombinase was expressed under the control of the Sox2 promoter confirmed that progenitor cells were recruited to the fibrotic lesion in response to bleomycin, and that this did not occur in CCN2-knockout mice. The ability of serum to induce α-smooth muscle actin expression in skin progenitor cells required the presence of CCN2. CONCLUSION: Sox2-positive skin progenitor cells are required in order for bleomycin-induced skin fibrosis to occur, and CCN2 is required for the recruitment of these cells to the fibrotic lesion. Targeting stem cell recruitment or CCN2 may therefore represent a useful therapeutic approach in combating fibrotic skin disease.
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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 | 0.000 | 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 | 0.002 |
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