Plasma Fibronectin Released by Peritoneal Macrophages Promotes Remote Skin Wound Healing
Bibliographic record
Abstract
Abstract Background Large peritoneal macrophages (LPMs), located in the peritoneal cavity, are essential for local tissue repair. However, their contribution to tissue repair at distant sites remains unclear. Aims This study investigates the role of LPM activation in skin wound healing at remote sites Methods A novel mouse model combining peritoneal stimulation (PS) with a skin injury was used to assess LPM-mediated effects on remote skin wound healing. Dual Cre and Flippase fate-mapping tracked GATA6-expressing LPMs to evaluate their migratory behavior. Parabiosis experiments and administration of activated peritoneal fluid were conducted to identify the role of circulating factors. Proteomic and transcriptomic analyses were used to characterize LPM-secreted molecules. Fluorescently labelled fibronectin was tracked in plasma and skin wounds. Results Activation of LPMs trough PS significantly accelerated healing of remote skin wounds. Removing LPMs or using mice lacking LPMs abolished the beneficial effect. Adoptive transfer of LPMs but not B-cells after LPM depletion was sufficient to rescue the phenotype. Fate-mapping demonstrated that LPMs did not migrate to distant wounds after activation. Parabiosis and peritoneal fluid transfer experiments indicated the role of LPM-derived circulating signaling molecules in remote skin wound healing. Proteomic and transcriptomic analyses identified fibronectin as critical mediator, as adoptive transfer of LyzMcre Fnflox peritoneal cells failed to rescue the impaired remote wound healing phenotype in LPM deficient mice. Protein-coding fibronectin isoforms transcribed by LPMs, correspond to the soluble plasma. Fluorescently labelled fibronectin was detected in the plasma and incorporated into skin wounds following adoptive transfer of Fngfp/gfp peritoneal cells and PS. Conclusion LPMs act as a source of circulating fibronectin, facilitating extracellular matrix formation and promoting wound healing at remote sites. These findings reveal a novel endocrine role for LPMs in systemic tissue repair, and challenge the traditional perspective, that plasma fibronectin is exclusively liver derived.
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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 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".