019 Stratifin-Induced MMP-1 in Fibroblast is Mediated by c-Fos and P38 MAPK Activation
Bibliographic record
Abstract
A delicate balance between synthesis of extracellular matrix (ECM) and degradation by matrix metalloproteinases (MMPs) is a key factor in maintaining the structural integrity of normal skin. Epidermal-mesenchymal interactions play a critical role in controlling the expression of MMPs during development and healing of skin. Disruption of this interaction increases the frequency of developing fibrotic conditions such as hypertrophic scarring and keloids. In the absence of epithelialization, ECM continues to accumulate until dermal fibroblasts receive signal(s) from epidermal cells to slow down the dynamic process of maturation and remodeling of the healing wound. We have recently demonstrated that keratinocyte releasable stratifin stimulates MMP-1 expression in dermal fibroblasts. However, the molecular mechanism by which stratifin protein induces MMP-1 expression in fibroblasts is unknown. Therefore, the purpose of the present study is to identify elements of the signaling pathway mediating stratifin stimulation of fibroblast MMP-1 expression. We did so by examining the three distinct MAPK pathways: ERK1/2, JNK, and p38 as well as the expression of the main components of the AP-1 dimers, c-Jun and c-Fos, which are mediated by distinct MAPK pathways. Our data shows that treatment of fibroblasts with stratifin resulted in rapid and transient up-regulation of c-jun and c-fos mRNA levels. Furthermore, we show that stratifin activates fibroblast MMP-1 expression at the mRNA and protein levels and this is mediated by p38 MAP kinase. Subsequent cDNA microarray analysis of fibroblasts treated with stratifin show an increase in a ternary complex factor, Sap-1. In conclusion, our results describes the mechanism by which stratifin activates MMP-1 in fibroblast, and demonstrates that p38 MAP kinase is an important regulator of MMP-1 gene expression involved in epidermal-mesenchymal interactions in wound remodeling. Acknowledgment: This work was supported by the Canadian Institute of Health Research (CIHR).
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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".