Porcine Epidemic Diarrhea Virus, a Member of the <i>Coronaviridae</i> Family, Increases Epithelial Secretion in the Jejunum by Up‐regulation of KCNN4
Notice bibliographique
Résumé
The porcine epidemic diarrhea virus (PEDV), an alphacoronavirus affects the small intestine of suckling piglets causing acute watery diarrhea. Here, the effects on agonist‐induced electrogenic secretory response by PEDV was assessed to determine its role in the diarrheal disease. Jejunal tissues were compared in healthy (n=12) and diseased (n=20) one‐week‐old crossbred Yorkshire x Landrace piglets in Ussing chambers. Diseased jejunal tissues displayed elevated changes in I sc following agonist addition compared to control. Activation of cAMP driven secretion via isoproterenol (adrenergic agonist) and forskolin/3‐isobutyl‐1‐methylxanthine (IBMX) demonstrated a significantly increased change in short‐circuit current ( I sc ). Cholinergic activation of secretion via carbachol revealed no significant difference in I sc , however, 9/20 diseased jejunal tissues had a negative change in I sc while the remaining 11/20 had a positive change in I sc . Bumentanide inhibitable I sc was not significantly different in diseased tissues compared to controls. Inhibition of cAMP induced secretion via glibenclamide revealed a significant increase in I sc , while niflumic acid, a potent inhibitor of calcium‐activated chloride channels, had no significant effect. Non‐selective potassium channel blocker tetraethylammonium chloride (TEA) revealed a significant decrease in the I sc of diseased animals compared to control. Furthermore, significant decrease in transepithelial electrical resistance (TEER) was noted in jejunal tissues infected with PED virus compared to controls. RT‐qPCR was conducted to determine if elevated chloride and potassium channel gene transcripts were responsible for the increase in cAMP induced secretion. Inflammatory cytokines were also assessed to determine their role in ion channel modulation. mRNA expression of the Cystic Fibrosis transmembrane conductance regulator (CFTR) in the jejunum of PEDV infected piglets was not significantly different than control, while potassium voltage‐gated channel subfamily Q member 1 (KCNQ1) was significantly down‐regulated in diseased animals. However, mRNA expression of potassium calcium‐activated channel subfamily N member 4 (KCNN4) and Transmembrane member protein 16A (TMEM16A) were significantly up‐regulated 3‐fold ( P < 0.05) and 5‐fold ( P < 0.05) respectively in the jejunum of diseased pigs compared to control. Furthermore, gene expression of proinflammatory cytokines was determined to be significantly elevated in the jejunum of diseased piglets. Collectively, these findings suggest that upregulation of KCNN4 by proinflammatory cytokines is responsible for the increased change in agonist induced I sc by driving chloride secretion via CFTR and TMEM16A. Support or Funding Information This research was supported by Genome Alberta GAB‐PEDH ‐ U of S – 344078, the Saskatchewan Agricultural Development Fund (ADF) Project 20140215, and the National Sciences and Engineering Research Council of Canada Discovery Grant 371364‐2010 (M.E.L.) This abstract is from the Experimental Biology 2018 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) | 0,000 | 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 ».