Correlation of cellular expression with function of NO‐sensitive guanylyl cyclase in the murine lower urinary tract
Notice bibliographique
Résumé
Key points Diseases of the lower urinary tract are associated with dysfunctions of cellular mechanisms that regulate smooth muscle tone. Nitric oxide (NO) mediates relaxation of most smooth muscle‐containing tissues via NO‐sensitive guanylyl cyclase (NO‐GC). Correlation of cellular localization with function of NO‐GC in the murine lower urinary tract has not been previously performed. Using cell‐specific knock‐out mice, we demonstrate that NO‐GC is expressed exclusively in smooth muscle cells of the urethral sphincter and mediates NO‐induced relaxation. In bladder detrusor, NO‐GC is not detected in smooth muscle cells but rather in platelet‐derived growth factor receptor α‐positive interstitial cells. NO‐GC in these cells does not contribute to NO‐induced relaxation; therefore, bladder detrusor smooth muscle appears to be unique as it is not relaxed by NO. The correlation of NO‐GC localization and function regarding smooth muscle relaxation allows the clinical use of compounds acting within NO/cGMP signalling to be assessed. Abstract The action of nitric oxide (NO) to stimulate NO‐sensitive guanylyl cyclase (NO‐GC), followed by production of cGMP, and eventually to cause smooth muscle relaxation is well known. In the lower urinary tract (LUT), in contrast to the cardiovascular system and the gastrointestinal tract, specific localization in combination with function of NO‐GC has not been investigated to date. Consequently, little is known about the mechanisms regulating relaxation of the lower urinary tract in general and the role of NO‐GC‐expressing cells in particular. To study the distribution and function of NO‐GC in the murine lower urinary tract, we used internal urethral sphincter and bladder detrusor from global (GCKO) and smooth muscle cell‐specific (SM‐GCKO) NO‐GC knock‐out mice for immunohistochemical analyses and organ bath experiments. In urethral sphincter, NO‐GC‐positive immunofluorescence was confined to smooth muscle cells (SMCs). Deletion of NO‐GC in SMCs abolished NO‐induced relaxation. In bladder detrusor, exposure to NO did not cause relaxation although immunohistochemistry uncovered the existence of NO‐GC in the tissue. In contrast to the urethral sphincter, expression of NO‐GC in bladder detrusor was limited to platelet‐derived growth factor receptor α (PDGFRα)‐positive interstitial cells. In conclusion, NO‐GC found in SMCs of the urethral sphincter mediates NO‐induced relaxation; bladder detrusor is unique as NO‐GC is not expressed in SMCs and, thus, NO does not induce relaxation. Nevertheless, NO‐GC expression was found in PDGFRα‐positive interstitial cells of the murine bladder with an as yet unknown function. Further investigation is needed to clarify the role of NO‐GC in the detrusor.
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 distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 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 | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
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 tête enseignante, 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 ».