A165 FCGBP IN THE COLON IS SPATIALLY DEPENDENT ON MUC2 EXPRESSION AND IS DEGRADED IN DEXTRAN SULFATE SODIUM-INDUCED COLITIS
Notice bibliographique
Résumé
Abstract Background The colonic mucus bilayer is an integral innate host defense mechanism that provides a physical barrier separating the lumen and its contents from the underlying epithelium. This essential barrier is produced by specialized secretory goblet cells of which Muc2 mucin is its primary product. IgG-Fc-binding protein (Fcgbp) is the second most abundant protein produced by goblet cells, which has a suggested function of crosslinking with Muc2 to stabilize the structural integrity of mucus. FCGBP is observed to decrease preceding the onset of inflammation in ulcerative colitis patients, leading to spatially distinct structural mucus weakening to contribute to the pathogenesis of the disease. Purpose Fcgbp is altered regionally in the gut and plays a role in the pathogenesis of dextran sulfate sodium (DSS)-induced colitis. The specific aims are: To characterize the spatial expression of Muc2 and Fcgbp basally in goblet cells To quantify alterations in Muc2 and Fcgbp in response to DSS-induced colitis and at restitution of disease Method mRNA and protein expression in Muc2+/+ and Muc2-/- C57BL/6 littermates were analyzed by RT-qPCR and Western blotting, respectively. Mucin granules were isolated from colonic goblet cells and the proteome quantified by liquid chromatography and tandem mass spectrometry (LC-MS/MS). Colitis was induced in Muc2+/+ mice with 3.5% (w/v) DSS in tap water for five days, whereas Muc2-/- littermates were given 1.5% (w/v) DSS in tap water for three days, ad libitum. Mice were given regular tap water for the remainder of the experiment to allow restitution of inflammation. Disease activity index (DAI) was scored based on weight loss. Mice were sacrificed at various time points up to 10 days, and colons excised and sectioned for histopathology analysis. Result(s) LC-MS/MS of mucin granules run under reducing and non-reducing conditions confirmed that Muc2 and Fcgbp were the most abundant proteins in mucin granules and were non-covalently bound to each other. mRNA and protein expression of Muc2 and Fcgbp were highly expressed in the mid colon, and regulation of Fcgbp was unaffected in Muc2-/- littermates. In response to DSS-induced colitis in Muc2+/+ mice, Muc2 transcription rapidly increased in all regions of the colon with highest expression in the mid colon. In contrast, Fcgbp transcription increased in the mid and distal colons and peaked during highest disease activity. Interestingly, Fcgbp protein expression was abrogated in the mid colon even at restitution. In Muc2-/- mice, Fcgbp transcription decreased during disease onset but returned to normal levels following removal of DSS. Image Conclusion(s) This study demonstrates that in response to DSS, Fcgbp expression was spatially degraded at the onset of disease and remained low at restitution. The disappearance of Fcgbp in the mid colon of Muc2+/+ littermates, despite Muc2 restoration, suggests that the mucus barrier remains structurally altered and functionally impaired at restitution. Supported by CIHR Disclosure of Interest None Declared
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 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 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 ».