Annexin <scp>A2</scp> Contributes to Release of Extracellular Vimentin in Response to Inflammation
Bibliographic record
Abstract
ABSTRACT Vimentin, an abundant intracellular cytoskeletal protein, is secreted into the extracellular space, where it can amplify tissue destruction in inflammatory diseases. The mechanisms by which inflammation promotes the release of extracellular vimentin (ECV) are not defined. In human subjects, we found > twofold higher levels of ECV in gingival crevicular fluid from periodontitis sites with inflammation compared with healthy sites. In cultures of human gingival fibroblasts (hGFs) treated with 1% serum or IL‐1β (10 ng/mL) to model tissue injury or inflammation, respectively, we found that 1% serum increased ECV release > 11‐fold while IL‐1β further enhanced release 17‐fold. Mass spectrometry of vimentin immunoprecipitates identified Annexin A2 (AnxA2), a Ca 2+ ‐dependent phospholipid‐binding protein, as a potential binding protein of ECV, which was confirmed by immunoprecipitation of cultured hGFs and immunostaining of inflamed human gingiva. IL‐1β treatment enhanced the abundance of AnxA2 and vimentin in membrane fractions prepared by sucrose gradients of hGF lysates. IL‐1β increased colocalization of ECV and AnxA2 at the outer aspect of the plasma membrane of intact hGFs. Knockdown of AnxA2 with siRNA or inhibition of the unconventional secretory pathway reduced ECV release from hGFs. These findings indicate that the production of ECV by hGFs in response to inflammation is mediated by an AnxA2‐dependent, unconventional secretory pathway that may play a role in amplification of the inflammatory response.
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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 | 0.002 | 0.001 |
| 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".