MP03-04 SECRETION OF NEUROTROPHINS AND THEIR PRECURSORS IS UNDER CONTROL OF NATRIURETIC PEPTIDE A IN BLADDER CELLS IN CULTURE
Bibliographic record
Abstract
You have accessJournal of UrologyCME1 Apr 2023MP03-04 SECRETION OF NEUROTROPHINS AND THEIR PRECURSORS IS UNDER CONTROL OF NATRIURETIC PEPTIDE A IN BLADDER CELLS IN CULTURE Claudia Covarrubias, Philippe Cammisotto, and Lysanne Campeau Claudia CovarrubiasClaudia Covarrubias More articles by this author , Philippe CammisottoPhilippe Cammisotto More articles by this author , and Lysanne CampeauLysanne Campeau More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003214.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Urine storage and bladder voiding are under control of the peripheral and central nervous systems. Neurotrophins, such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), controls neuroregeneration while their respective precursor proNGF and proBDNF trigger inflammatory processes and apoptosis. The ratio between neurotrophins to proneurotrophins must therefore be tighly controlled and constitutes a viable biomarker for overactive bladder syndrome (OAB). On the other hand, natriuretic peptide A (ANP) that is increased during aging, has been linked to OAB. We here examine how ANP is involved in the secretion of neurotrophins by cells of the bladder. METHODS: Smooth muscle (SMC) and urothelial cells (URO) were grown from rat bladder after collagenase digestion. After confluency, they were incubated for 24 hours with ANP (100 nM). NGF, proNGF, BDNF, proBDNF and matrix metalloproteinase-9 (MMP-9) were measured using specific kits. RESULTS: We found that both cell types are major source of NGF and proNGF while BDNF and proBDNF were mainly released by SMC. ANP decreases NGF and proBDNF secretion by SMC, while proNGF and BDNF levels were not affected, mimicking the observations obtained in urine samples of a female cohort of patients diagnosed with OAB. Interestingly, ANP also increased MMP-9 activity in the same cell culture medium. In UROs, no changes in the secretion of neurotrophins or proneurotrophins could be observed, however, the secretion of active MMP-9 was found potently enhanced by ANP with final levels around 20 times higher than the ones found in SMC medium. Finally, using CrisprCas9 to knockdown MMP-9 gene, we confirmed the essential role of this enzyme in the proteolysis of NGF into peptides and in the conversion of proBDNF to BDNF. CONCLUSIONS: Bladder cells exhibit unique pattern of neurotrophin secretions. Both are affected by ANP, SMC mostly at the level of neurotrophin secretions and urothelial cells in the amount of MMP-9 released in the extracellular medium. We suggest that the imbalance in neutrophin ratios observed in the urine of patients with OAB could result, at least in part, from a direct action of ANP on bladder cells. Source of Funding: Canadian Urologist Association and Quebec Network for Research on Aging (RQRV) © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e22 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Claudia Covarrubias More articles by this author Philippe Cammisotto More articles by this author Lysanne Campeau More articles by this author Expand All Advertisement PDF downloadLoading ...
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.014 | 0.005 |
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".