High MUC2 Production in Goblet Cells Induces ER Stress and Exhibit Increase Susceptibility to Apoptosis
Bibliographic record
Abstract
MUC2 is a large glycoprotein produced by goblet cells (GC) that form the protective mucus blanket overlying the intestinal epithelium. During pathological conditions such as IBD or colonic cancers, MUC2 biosynthesis and secretion are accelerated. Little information is known on how MUC2 production is regulated and whether GC undergoes endoplasmic reticulum (ER) stress following high MUC2 biosynthesis. We studied the role of MUC2 in GC stress using a high MUC2 producing GC line, HT29‐H, and a clone of HT29‐H (HT29‐L) in which MUC2 was stably silenced using lentivirus shRNA. Cells were treated with the ER stressor, tunicamycin (TUN) and markers for ER stress (GRP78, ATF4, CHOP, sXBP1) and apoptosis (caspase 3 and PARP cleavage) quantified by western blotting and RT‐qPCR. Compared to HT29‐L, HT29‐H cells showed significant increase in ER stress and apoptosis in response to TUN. Over expressing MUC2 in non‐MUC2‐producing SKCO15 cells also increased ER stress and apoptosis confirming specificity of MUC2. Pre‐treatment of cells with reactive oxygen species (ROS) inhibitor, diphenyleneiodonium, abrogated basal stress levels, TUN‐induced ER stress and apoptosis. HT29‐H constitutively produced significantly more ROS than HT29‐L cells indicating that high MUC2 production specifically increases ROS production that drives ER stress and apoptosis. These findings were corroborated in isolated colonic epithelial cells and colonic tissues from Wt and Muc2 ‐/‐ mice that showed significant increase in ER stress in Wt as compared to Muc2 ‐/‐ mice. We conclude that high MUC2 production by GC induces ER stress and apoptosis that could subsequently lead to diminished mucus barrier function in disease pathogenesis. Grant: CIHR
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".