A85 SEMAPHORIN-3E AMELIORATES INTESTINAL INFLAMMATION BY REGULATING EXPRESSION OF TIGHT JUNCTION PROTEIN AND PROINFLAMMATORY MEDIATORS
Bibliographic record
Abstract
Ulcerative colitis (UC) is characterized by an alterations of tight junction (TJ) barrier and immune responses that result in abnormal passages of exogenous antigens such as gut-derived bacterial lipopolysaccharides (LPS). Semaphorin-3E (Sema3E) and its receptor plexin D1 (PLXD1R) are key regulators of epithelia and immune systems To investigate Sema3E activity in human and animal model of colitis and its effects on the intestinal epithelial cell functions Sema3E mRNA level and its correlation with TJ proteins and mucosal healing mediator (Krupple-Like Factor [KLF]-5) were quantified in human rectal biopsies. PLXD1R expression was quantified by immunofluorescence/RT-qPCR in Caco2 epithelial cell line and mice colonic tissues. Proliferation, metabolism, viability and wound healing properties were evaluated after 24 hours of treatment with Sema3E recombinant protein (100ng/ml). TJ proteins and KLF-5 were quantified by RT-qPCR in Caco-2 cells pretreated with Sema3E for 24 h and challenged with LPS (1μg/ml) for additional 24 h. Dextran sulfate sodium (DSS)-colitis was induced in BL6/57 mice for 5 days. Sema3E treatment (10µg/kg/day/intra-peritoneal) started at day 5 after induction of colitis and lasted for 4 days. Disease activity index (DAI), macroscopic and histological scores were assessed. mRNA and protein levels of pro-inflammatory cytokines and KLF5 were quantified. Sema3E is reduced in active and mild UC patients and has strong positive correlation with CLDN1 (r = 0.54, P =0.03), ZO-1 (r = 0.53, P = 0.03), CADH1 (r = 0.60, P =0.01), OCLDN (r = 0.64, P =0.008), KLF-5 (r = 0.52, P =0.03), TLR2 (r = - 0.6147, P =0.0103) and TLR4 (r = - 0.5794, P =0.0207). PLXD1R is expressed by Caco2 cells and mice colonic tissue. Sema3E accelerated significantly the epithelial cells migration when compared to control group. No significant changes on epithelial cells proliferation, metabolism and viability were detected. Compared to LPS-induced inflammation, Sema3E treatment increased the expression levels of TJ proteins (Cldn1, Zo-1, ECadh1, Ocldn) and Klf5, and decreased Tlr2 without significant changes in Tlr4. Sema3E treatment decreases DAI, macroscopic and histological scores in DSS-induced colitis compared with control. Il6 and Mcp1 were significantly decrease in colitic mice treated with Sema3E when compared to untreated mice. Il1bTnfa tend to decrease whereas Klf5 tends to increase. No changes in colonic levels of Tlr2, Tlr4, Cldn1, Zo-1 and Ocldn were detected. Sema3E regulates intestinal inflammation through epithelial cells barrier markers in human and cell line and reduces experimental inflammation and proinflammatory mediators. These findings may lead to improved therapeutic strategies in the treatment of UC by restoring Sema3E level in UC patients. CCC, CIHR
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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".