Cyclosporin inhibition of collagen remodeling is mediated by gelsolin
Bibliographic record
Abstract
Cyclosporin A (CsA) inhibits collagen remodeling by interfering with the collagen-binding step of phagocytosis. In rapidly remodeling connective tissues such as human periodontium this interference manifests as marked tissue overgrowth and loss of function. Previous data have shown that CsA inhibits integrin-induced release of Ca(2+) from internal stores, which is required for the binding step of collagen phagocytosis. Because gelsolin is a Ca(2+)-dependent actin-severing protein that mediates collagen phagocytosis, we determined whether gelsolin is a CsA target. Compared with vehicle controls, CsA treatment of wild-type mice increased collagen accumulation by 60% in periodontal tissues; equivalent increases were seen in vehicle-treated gelsolin-null mice. Collagen degradation by phagocytosis in cultured gelsolin wild-type fibroblasts was blocked by CsA, comparable to levels of vehicle-treated gelsolin-null fibroblasts. In wild-type cells treated with CsA, collagen binding was similar to that of gelsolin-null fibroblasts transfected with a gelsolin-severing mutant and treated with vehicle. CsA blocked collagen-induced Ca(2+) fluxes subjacent to bound collagen beads, gelsolin recruitment, and actin assembly at bead sites. CsA reduced gelsolin-dependent severing of actin in wild-type cells to levels similar to those in gelsolin-null fibroblasts. We conclude that CsA-induced accumulation of collagen in the extracellular matrix involves disruption of the actin-severing properties of gelsolin, thereby inhibiting the binding step of collagen phagocytosis.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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".