TRPV4 receptor as a functional sensory molecule in bladder urothelium: Stretch‐independent, tissue‐specific actions and pathological implications
Bibliographic record
Abstract
Abstract The newly recognized sensory role of bladder urothelium has generated intense interest in identifying its novel sensory molecules. Sensory receptor TRPV4 may serve such function. However, specific and physiologically relevant tissue actions of TRPV4, stretch‐independent responses, and underlying mechanisms are unknown and its role in human conditions has not been examined. Here we showed TRPV4 expression in guinea‐pig urothelium, suburothelium, and bladder smooth muscle, with urothelial predominance. Selective TRPV4 activation without stretch evoked significant ATP release—key urothelial sensory process, from live mucosa tissue, full‐thickness bladder but not smooth muscle, and sustained muscle contractions. ATP release was mediated by Ca 2+ ‐dependent, pannexin/connexin‐conductive pathway involving protein tyrosine kinase, but independent from vesicular transport and chloride channels. TRPV4 activation generated greater Ca 2+ rise than purinergic activation in urothelial cells. There was intrinsic TRPV4 activity without exogeneous stimulus, causing ATP release. TRPV4 contributed to 50% stretch‐induced ATP release. TRPV4 activation also triggered superoxide release. TRPV4 expression was increased with aging. Human bladder mucosa presented similarities to guinea pigs. Overactive bladders exhibited greater TRPV4‐induced ATP release with age dependence. These data provide the first evidence in humans for the key functional role of TRPV4 in urothelium with specific mechanisms and identify TRPV4 up‐regulation in aging and overactive bladders.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| 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".