Porcine Epidemic Diarrhea Virus, a Member of the <i>Coronaviridae</i> Family, Increases Epithelial Secretion in the Jejunum by Up‐regulation of KCNN4
Bibliographic record
Abstract
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 .
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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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".