157 - Nerve growth factor synthesis from rat bladder cells is sex-specific
Bibliographic record
Abstract
Hypothesis / aims of study Nerve Growth Factor (NGF) is essential in the development and survival of cells of the nervous system. In a cohort of female aging patients diagnosed with overactive bladder (OAB), its urinary levels are low compared to healthy controls. High activity of the enzyme matrix metalloproteinase-9 (MMP-9), the main protease that degrades NGF into inactive peptides was oberved in the same samples. Murine diabetic models with bladder dysfunction also display low NGF content in bladder tissue with elevated MMP-9. Chronic treatment of these mice with THX-B, an antagonist of the pro-inflammatory receptor p75NTR, restored NGF levels in bladder and improved detrusor contractile activity. MMP-9 levels were decreased by THX-B only in female. We aim here to understand the differences in NGF synthesis between male and female bladder cells. Study design, materials and methods Smooth muscle (SMC) and urothelial (URO) cells were isolated from male and female sprague-Dawley rat bladders after collagenase IV digestion. Cells were incubated for 24 hours with THX-B (5 microg/mL) or the nitric oxide generator sodium nitroprusside (SNP, 300 microM). Cell extracts and culture medium were analyzed using Elisa kits (NGF and proNGF), enzyme activity (MMP-9, furin, plasmin) by enzymatic kits, RTqPCR and immunoblotting for cell proteins. Results THX-B led to an increase in NGF secretion from male and female urothelial cells while proNGF was increased in male only. No changes by THX-B was observed in SMC in both gender. SNP decreased NGF secretion in URO and SMC in female cells only. On the other hand, THX-B and SNP respectively decreased and increased MMP-9 activity in female cells while male cells were unaffected by both treatment. NGF mRNA levels were unaffected in both gender. Proteolytic enzymes converting proNGF into NGF, namely plasmin, MMP-7, MMP-3 and furin, were increased by SNP and THX-B in female cells while the same enzymes were decreased in male cells, suggesting other post-translational point of controls of mature NGF synthesis in the latter. Interpretation of results Sex-specific processing of neurotrophins has been observed in other pathologies such as Alzheimer's disease. Interestingly, the same proteases appear to be involved in LUTS. Concluding message These data confirmed that the mechanisms regulating the secretion of NGF and proNGF in rats is sex-specific and relies on different pathways of synthesis. These data should be taken into account when considering OAB in male and female patients. Funding Canadian Urological Association Clinical Trial No Subjects Animal Species rat Ethics Committee Canadian Council for Animal Care and Animal Ethics Committee of McGill University (Quebec, Canada).
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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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.006 | 0.002 |
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".