Robust pan-junctional reinforcement preserves the gut epithelial barrier under mechanical stress
Bibliographic record
Abstract
Abstract Epithelia are specialized tissue barriers that safeguard the organism’s internal milieu from the hostile external environment, a function critically dependent on intercellular junctions. In the colon, this barrier is repeatedly challenged by mechanical distension from faeces and it is unknown whether and how the colon adapts to such stress, which could otherwise compromise barrier integrity. Here, we show that faeces-mediated mechanical distension triggers coordinated remodelling at cell- and tissue-scale, suggestive of mechanoadaptation. This response includes recruitment of junctional proteins at all three types of adhesive cell-cell junctions (tight junctions, adherens junctions and desmosomes). We identified two modes of recruitment: stable responders (ZO-1, E-cad, plakoglobin) with sustained junctional enrichment, and adaptive responders (desmoplakin, keratin 8) with progressive accumulation during distension. Distension was also accompanied by perijunctional recruitment and activation of non-muscle myosin II (NMMII). Through genetic, pharmacological, and mechanical perturbations, we demonstrated that NMMII activation is an early and critical step for mechanoadaptation. This process requires extracellular calcium influx, and Piezo1 activation is sufficient to trigger NMMII activation and junctional recruitment. Loss of NMMII function abrogated the junctional response to distension across all three junctional complexes, including desmosomes, resulting in disorganised junctions and barrier breach. Together, our findings uncover a robust physiological mechano-adaptive response of the adult colonic epithelium to an extrinsic mechanical stress, whereby coordinated reinforcement of all junctional complexes, controlled by myosin II and mechanosensitive calcium influx, plays an essential role in preserving intestinal barrier integrity.
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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) | 0.001 | 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".