P033 Periostin regulates ER-stress mediated intestinal subepithelial myofibroblasts function to promote fibrosis in Crohn’s disease
Bibliographic record
Abstract
Periostin is a secreted matricellular protein and a major component of the extracellular matrix (ECM) that contributes to intestinal fibrosis in the patients with fibrostenotic Crohn’s disease. Currently, intestinal fibrosis has no efficient treatment. Previous studies showed that endoplasmic reticulum (ER) stress in intestinal epithelial cells plays a role in the pathogenesis of Crohn’s disease. ER stress is also involved in the development of other fibrotic diseases. Subepithelial myofibroblasts (SEMF) are key drivers of intestinal fibrosis. However, the role of periostin in SEMF during the ER stress-mediated intestinal fibrosis in Crohn’s disease remains unknown. SEMF will be isolated from the patients with each Crohn’s disease phenotype and placed into 3D organoid culture. Periostin expression in freshly isolated and cultured cells was determined by western blot and qRT-PCR. Its interaction with integrin αvβ3 was confirmed by proximity ligation hybridisation assay. Knockdown of periostin in cells was accomplished with siRNA. TGF-β1 was measured by ELISA. Proliferation was measured by WST-1 assay. Migration by wounding assay. Periostin expression increased 9.3 ± 0.4 fold in vimentin staining-positive SEMF isolated from affected ileum of fibrostenotic Crohn’s disease (Montreal B2) compared with normal ileum in the same patient. Periostin protein was not detected in patients with other phenotypes (Montreal B1 or B3). In the presence of 10 ng/ml IL-6 significantly increased periostin protein expression and its interaction with integrin αvβ3 in SEMF compared with controls. ER stress induced by tunicamycin elicited cell proliferation and enhanced migration was inhibited by 51 ± 3.1% and 53 ± 2.6% when periostin was knocked down in SEMF compared with scrambled controls. In addition, αvβ3-dependent activation of latent TGF-β1 was inhibited by 40 ± 2.1% and 25 ± 2.3% with knockdown of periostin in both control cells and cells with subjected to ER Stress. Periostin promotes SEMF proliferation and migration. Periostin interacts with integrin αvβ3 and regulates latent TGF-β activation during ER stress-induced fibrosis.
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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) | 0.003 | 0.001 |
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".