Short Chain Fatty Acid Transporter/Receptor Expression and Signaling in Enteric Glial Cells
Bibliographic record
Abstract
The enteric nervous system (ENS) independently coordinates gastrointestinal functions such as motility, secretion, and absorption. Enteric glial cells (EGCs), the largest group of cells within the ENS, secrete neurotrophic factors that support enteric neurons and epithelial growth factors that promote integrity of the intestinal epithelial barrier. Although numerous studies have examined the effect of short chain fatty acids (SCFAs) on functional properties of several intestinal cell types, including enterocytes, enteroendocrine cells, and gut immune cells, no studies to date have examined if and how SCFA influence EGCs. We sought to determine: (1) if EGCs have the capacity to respond to SCFAs; (2) signaling pathways downstream of SCFA transporters/receptors are active in EGCs. Experiments were performed in a stably transformed enteroglial cell line (Ruhl et al., 1998). Cells were treated with propionate (0–10 mM), butyrate (0–5 mM), AR420626 (an FFAR3 agonist), or an FFAR2 agonist. Activation of transporters and receptors was assessed using Western blotting for acetylation and phosphorylation state of proteins downstream of the receptors. Expression of SCFA transporters and receptors was assessed using quantitative PCR. Basal expression of monocarboxylate transporter (MCT)-1 and MCT-4, as well as the G-protein coupled receptors FFAR2 and FFAR3 was detected, with expression levels of MCT-1 the highest. GPR109a and Olfr920 were not present in these cells. Butyrate treatment for 2 hours significantly elevated levels of acetylated histone H2B and H3 (P < 0.05), but not histone H2A, suggesting that this SCFA is transported across the plasma membrane to exert intracellular effects. Neither SCFAs nor AR420626 blocked forskolin-induced phosphorylation of protein kinase A (PKA), suggesting that FFAR3 signaling is not active in EGCs. Butyrate, but not the FFAR2 agonist, significantly increased phosphorylation of protein kinase C (PKC) (P < 0.05), suggesting that signaling pathways independent of FFAR2 are triggered by SCFA in EGCs. Our preliminary evidence suggests that SCFAs are internalized by EGCs and affect intracellular signaling events. Future studies will determine the implications of histone deacetylation and PKC activation by SCFA on EGC function. University of Winnipeg Major Research Grant.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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) | 0.000 | 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 teacher head, 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".