Modulation of Intestinal Epithelial Barrier Function by Rhamnogalacturonan
Notice bibliographique
Résumé
Background The Inflammatory Bowel Diseases (IBD) are chronic inflammatory disorders of the gastrointestinal tract and are associated with changes in intestinal epithelial barrier function. However, despite several effective therapeutic options, many patients become refractory to the treatment and adverse effects have been reported. For this reason, the development of new drugs targeting the epithelial barrier function is essential. Recently, polysaccharides isolated from plants and fungi have emerged as an important class of natural products with immunomodulatory, anti‐inflammatory and wound healing activity. Previous studies showed that rhamnogalacturonan (RGal), a polysaccharide isolated from Acmella oleracea , protected mice against colitis induced by dextran sulfate sodium (DSS). However, the exact mechanism of action of RGal are not fully clarified. We hypothesized that RGal modulates the intestinal epithelial barrier function and assessed the signaling pathways involved in RGal effect. Methods Human colonic epithelial Caco‐2 cells were seeded on Snapwells, grown for 6 days, and mounted in Ussing chambers to measure the epithelial barrier function [transepithelial electrical resistance (TER) and FITC‐dextran permeability]. Cells were apically treated with RGal (10–1000 μg/ml) after 30 min of FITC‐dextran addition. In a calcium‐switch assay, the epithelial monolayers were temporarily exposed to zero calcium conditions (calcium‐free buffer containing the calcium chelator, EGTA) to disassemble tight junctions. RGal (10–1000 μg/ml) was added during calcium‐free conditions. The FITC‐dextran permeability was also evaluated in Caco‐2 cells stimulated with IFNg plus TNF‐a (25 ng/ml, basolateral) and treated with RGal (1000 μg/ml, apical) every 24 h for 48 h. To evaluate the signaling pathways, the cells were pre‐treated with selective inhibitors of MEK1/2, p38 or PI3K 30 minutes before RGal addition. Results Apical addition of RGal at concentration of 1000 μg/ml significantly increased TER in 185% and caused a 64% reduction in FITC‐dextran flux compared to control group. In addition, RGal also was able to accelerate the tight junction reassembly in 155% during a reversible barrier disruption induced by calcium depletion. When the barrier disruption was caused by cytokines, RGal (1000 μg/ml) significantly reduced the FITC‐dextran flux by 33 and 24% at 30 and 60 min, respectively. However, the signaling pathway inhibitors did not reverse the RGal effect on TER suggesting that MAPkinase and PI3K pathways were not involved. Conclusions These findings demonstrated that RGal increases intestinal epithelial barrier function which appears to be due to effects on tight junction assembly. Further experiments will be carried out to determine the tight junction proteins and signaling pathways are involved in the RGal effect. Elucidation of RGal mechanisms of action could lead to new approaches to the treatment of IBD. Support or Funding Information Dr. Baggio is supported by an Eyes High postdoctoral fellowship from the University of Calgary. Her research project is funded by a grant from Crohn's and Colitis Canada.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».