MP49-04 MATRIX METALLOPROTEINASE-9 CONTROLS SECRETION OF NERVE GROWTH FACTOR FROM BLADDER CELLS IN VITRO
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You have accessJournal of UrologyCME1 May 2022MP49-04 MATRIX METALLOPROTEINASE-9 CONTROLS SECRETION OF NERVE GROWTH FACTOR FROM BLADDER CELLS IN VITRO Aya Hajj, Aalya Hamouda, Stephanie Sirmakesyan, Philippe Cammisotto, and Lysanne Campeau Aya HajjAya Hajj More articles by this author , Aalya HamoudaAalya Hamouda More articles by this author , Stephanie SirmakesyanStephanie Sirmakesyan 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.0000000000002624.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Urine of female patients with overactive bladder syndrome (OAB) is characterized by low levels of the neurotrophin NGF with stable levels of its precursor proNGF. The resulting imbalance between NGF and proNGF may originate from an elevated activity of the proteolytic enzyme matrix metalloproteinase-9 (MMP-9) observed in the same samples. On the other hand, an inhibitor of the proinflammatory p75NTR receptor, THX-B, restored NGF levels to normal in a murine model of diabetic voiding dysfunction (Mossa et al 2020). The aim of the present work is to: 1) determine if NGF and MMP-9 are synthesized by cells of the bladder; 2) assess the role of MMP-9 in the synthesis and release of NGF by the same cells; and 3) examine how NGF secretion and MMP-9 might be affected by THX-B. METHODS: Rat bladders were digested by collagenase type IV to generate primary cultures of urothelial and smooth muscle cells. The expression of NGF, proNGF and MMP-9 were assessed by RT-qPCR and by immunoblotting. Cellular localisation of proteins was obtained by immunohistochemistry. Knock-down of MMP-9 was achieved using Crispr-Cas9. Levels of NGF and proNGF were measured by ELISA and enzyme activities by specific enzymatic kits. RESULTS: Urothelial and smooth muscle cells were found to contain and release significant amounts of NGF, proNGF and MMP-9 as revealed by RT-qPCR, immunoblotting and microscopy. The knock-down of MMP-9 using Crispr-Cas9 resulted in the disappearance of MMP-9 mRNA, proteins and enzymatic activity, in both cell types. In the MMP-9 knock-down cells, levels of secreted NGF were multiplied by a factor 4 to 9 while proNGF concentrations were not affected. On the other hand, incubation of urothelial cells with the p75 antagonist THX-B (5 µg/mL) for 24 hours increased NGF secretion and concomitantly decrease the activity of MMP-9. MMP-7, the enzyme converting proNGF to NGF, displayed an increased activity as well. On the other hand, THX-B had no effect on smooth muscle cells. Levels of mRNA were not affected by THX-B in both cell types. Pathways associated to p75NTR, namely erk, jnk, p38MAPK and cyclic AMP were also unchanged by treatment with THX-B. CONCLUSIONS: Bladder cells express, synthesize and release NGF, proNGF and MMP-9. The latter is central in the control of NGF secretion. THX-B targets urothelial cell to enhance NGF secretion by downregulation of MMP-9 and increased in MMP-7 activities, which could explain the improvement of diabetic voiding dysfunction in vivo. Source of Funding: Canadian Urology Association © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e854 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Aya Hajj More articles by this author Aalya Hamouda More articles by this author Stephanie Sirmakesyan More articles by this author Philippe Cammisotto More articles by this author Lysanne Campeau More articles by this author Expand All Advertisement PDF downloadLoading ...
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,021 | 0,005 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».