Lysophosphatidic acid and its receptors in the pathogenesis of rheumatoid arthritis
Bibliographic record
Abstract
Background Lysophosphatidic acid (LPA) is a bioactive lipid mediator that plays a central role in a broad ranges of physiological and pathological processes, through activating its G‐protein coupled receptors. It is worth noting that Autotaxin (ATX), an enzyme that produces the major part of extracellular LPA, is expressed at significantly higher levels in synoviocytes from patients with rheumatoid arthritis (RA). Whereas LPA was implicated in human tumorigenesis the RA synovium resemble the tumor phenotype with many features. Thus it is possible that LPA, via interacting with its receptors, plays a potential role in the pathogenesis of RA. Results We firstly discovered that the receptors for LPA, namely LPA1, LPA2, and LPA3, are all expressed in human synoviocytes; and the expression of LPA3 by synoviocytes is up‐regulated by the proinflammatory cytokine, TNF‐α. Our data also showed that exogenously applied LPA could stimulate the production of IL‐8 by synoviocytes, an important neutrophil chemotactic factor that can recruit inflammatory leucocytes to the inflammation sites. Finally, antagonists of LPA receptors, VPC32183, significantly inhibited LPA‐induced production of IL‐8. Conclusions These findings suggest that LPA, through the interaction with its receptors, would contribute to the pathogenesis of RA by stimulating inflammatory chemokine IL‐8. Our results provide novel insights into the expression of functional LPA receptors in synoviocytes. Since LPA receptor antagonists efficiently down‐regulate LPA‐mediated IL‐8 protein expression, the blockade of LPA receptor may offer potential for the treatment of RA. The source of research support Canadian Institutes of Health Research
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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 | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| 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".