Loss of Intestinal Epithelial AMPK Does Not Alter Susceptibility to Acute Chemical Colitis or Bacterial Infection
Notice bibliographique
Résumé
AMP‐Activated Protein Kinase (AMPK) is a master regulator of cellular energy status. Its primary actions are mediated by its alpha catalytic subunit, which has two isoforms. Previous evidence in mice has suggested that loss of an individual AMPK‐α isoform compromises critical functions of the intestinal epithelium such as tight junction permeability while intact AMPK activity is protective against mucosal inflammation. These processes are essential to maintain the intestinal barrier and prevent chronic inflammation. However, AMPK‐dependent effects under cellular stress conditions have not been consistent and appear context‐dependent. Additionally, published studies have not confirmed whether AMPK is necessary and sufficient for these effects. The goals of this study were to determine if AMPK is required to protect from mouse models of acute colitis. Methods Deletion of AMPKα specifically in intestinal epithelial cells was accomplished by crossing Prkaa1/2 floxed mice with Villin‐Cre mice. Dextran sulfate sodium (DSS) colitis was induced in conventionally housed intestinal epithelial cell‐specific AMPK knockout (AMPKα ΔIEC KO ) and AMPK floxed (AMPKα fl/fl ) mice. 40kDa DSS was administered at 2.5% in drinking water ad libitum for 5 days followed by 3 days of water. Disease activity index was calculated from daily measures of body weight, stool consistency, and presence of hemaoccult. On the day of sacrifice mice were orally gavaged with 4kDa FITC‐dextran and blood was collected after 4 hours to determine intestinal permeability. Mice were sacrificed and intestinal tissues were flash frozen. Citrobacter rodentium infection was performed in mice housed under specific pathogen‐free (SPF) conditions following overnight treatment of 50ng/mL streptomycin. Mice were orally gavaged with ~10 8 CFU of C. rodentium (DBS100 streptomycin‐resistant strain). Fecal bacterial load was determined regularly until sacrifice on day 10 post‐infection. Colon and extra‐intestinal tissues (mesenteric lymph nodes, spleen, and liver) were excised to determine bacterial burden. Results AMPKα ΔIEC KO mice did not exhibit increased susceptibility to 2.5% DSS compared to AMPKα fl/fl mice as determined by similar changes in body weight and disease activity index throughout the course of disease. In addition, there were no significant differences in colon weight or length after DSS (n = 4 – 15). AMPKα ΔIEC KO mice do not appear to have significantly increased intestinal permeability after DSS treatment. To test if AMPK is important for responses to enteric infection, mice were infected with Citrobacter rodentium , a mouse model of enteropathogenic (EPEC) and enterohemorrhagic E. coli (EHEC) infection in humans. Infected mice had identical increases in fecal bacterial burden over time (~10 7 CFU/g, n = 3–6) and loss of AMPK did not affect disease progression. In addition, AMPK deficiency did not increase bacterial invasion of extra‐intestinal tissues (n = 3–4). Conclusions These data suggest that AMPK plays only a minor role in intestinal epithelial function and suggests that protection from colitis is mediated by AMPK‐independent pathways. Support or Funding Information NIH 2R01DK091281 (DFM) This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
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) | 0,001 | 0,000 |
| Bibliométrie | 0,001 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,002 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,003 | 0,001 |
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 ».