Human Red Blood Cells Contain Antifibrogenic Factors That Stimulate MMP-1 Expression in Dermal Fibroblasts
Bibliographic record
Abstract
The healing of a burn injury is a dynamic biological process, and there must be a set of factors that gradually slow down and/or terminate this healing process upon epithelialization. We have previously demonstrated that some members of the 14-3-3 protein family including stratifin, which is mainly released by differentiated keratinocytes, have a potent matrix metalloproteinase-1 (MMP-1), -3, -8, and -24 stimulatory effect for fibroblasts. During the course of our studies, we discovered that human red blood cells (RBCs) contain a high level of different 14-3-3 isoforms. In this study, we evaluated the presence of these proteins in RBC and examined the efficacy of RBC in stimulating the expression of MMP-1 in dermal fibroblasts using Western blot analysis. The findings revealed the presence of all seven isoforms of 14-3-3 (η, γ, ε, σ, β, ζ, and τ) in RBC lysate, though with different levels of expression. Interestingly, the levels of some of these proteins were higher in RBC from new born babies compared to those of adults. We also found that RBC lysate significantly increased the expression of MMP-1 in different strains of fibroblasts, and this effect has been abrogated by almost 20% when R18 was used to deplete the 14-3-3 proteins from lysate. However, when RBC lysate was passed through a 3-kDa filter, and then whole RBC lysate, retentate, and filtrate were used to treat three strains of fibroblasts, MMP-1 expression was increased significantly, indicating the presence of MMP-1-inducing factors smaller than 3kDa in RBC lysate as well. The MMP-1 stimulatory effect of RBC lysate for fibroblasts was stable at freeze/thawing as well as freezing for at least 1 year. In conclusion, the MMP-1 stimulatory effect of RBC lysates might play an important role in the regulation of extracellular matrix under physiological and pathological conditions. Because of its MMP-1 stimulating effect, the RBC lysate might be used as an antifibrogenic factor for the treatment of some fibroproliferative conditions such as hypertrophic scarring and keloid.
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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) | 0.002 | 0.001 |
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".