Urokinase-Type Plasminogen Activator Plays Essential Roles in Macrophage Chemotaxis and Skeletal Muscle Regeneration
Bibliographic record
Abstract
Although macrophages are thought to play important roles in tissue repair, the molecular mechanisms involved remain to be elucidated. Mice deficient in urokinase-type plasminogen activator (uPA-/-) exhibit decreased accumulation of macrophages following muscle injury and severely impaired muscle regeneration. We tested whether macrophage-derived uPA plays essential roles in macrophage chemotaxis and skeletal muscle regeneration. Macrophage uPA was required for chemotaxis, even when invasion through matrix was not necessary. The mechanism by which macrophage uPA promoted chemotaxis was independent of receptor binding but appeared to depend on proteolytic activity. Exogenous uPA restored chemotaxis to uPA-/- macrophages and rescued muscle regeneration in uPA-/- mice. Macrophage depletion in wild-type (WT) mice using clodronate liposomes resulted in impaired muscle regeneration, confirming that macrophages are required for efficient healing. Furthermore, transfer of WT bone marrow cells to uPA-/- mice restored macrophage accumulation and muscle regeneration. In this rescue, transferred WT cells appeared to contribute to IGF-1 expression but did not fuse to regenerating fibers. These data indicate that WT leukocytes, including macrophages, that express uPA were sufficient to rescue muscle regeneration in uPA-/- mice. Overall, the results indicate that uPA plays a fundamental role in macrophage chemotaxis and that macrophage-derived uPA promotes efficient muscle regeneration.
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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) | 0.001 | 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".