Prostaglandin E <sub>2</sub> (PGE <sub>2</sub> ) function in pregnancy – New perspectives for the putatively pro‐quiescent downstream target RGS2
Notice bibliographique
Résumé
Background The prostaglandin pathway plays an important, but complex, role in human labour. Targeting this pathway to treat preterm labour is not wholly effective nor fully safe. Developing superior clinical approaches requires further understanding of the mechanisms that govern myometrial function in labour. While PGE 2 is implicated as a pro‐labour mediator, we have previously shown that it can also promote myometrial smooth muscle (MSM) relaxation. Some of these pro‐quiescent effects may result from PGE 2 ‐mediated upregulation of gene expression. Among the genes highly induced by PGE 2 is the regulator of G‐protein signalling 2 (RGS2), which has been shown to selectively turn‐off, G αq ‐coupled, G‐protein coupled receptor (GPCR) signaling. In pregnancy, G αq ‐coupled GPCRs in the MSM, such as the oxytocin receptor, activate uterine contractions in labour in a calcium‐dependent manner. We hypothesize that in the uterus RGS2 can regulate the G αq ‐coupled GPCR signals, that promote contractility giving rise to active labour. By attenuating these signaling pathways, we anticipate that RGS2 promotes quiescence of the uterus and may represent a novel mechanism by which PGE 2 regulates uterine function in pregnancy and labour. This mechanism may be clinically relevant in the management of labour. Objective To investigate the effect of PGE 2 on RGS2 expression, and examine possible roles for RGS2 in attenuating G αq ‐coupled GPCR contractile functions in primary human MSM cells. Methods Primary myometrial smooth muscle cells were isolated from myometrial biopsies from term (37–40 weeks of gestation), non‐labour caesarean section deliveries. Cultured cells were treated with PGE 2 (1 μM) to study effects on RGS2 mRNA and protein expression. The effect of RGS2 on calcium flux stimulated by oxytocin (100 nM) or histamine (1 μM) treatment was studied as a measure of contractility, using a Fluo‐4 calcium assay. Results were analyzed using a one‐way ANOVA (Bonferroni post‐hoc ). Results In MSM cells PGE 2 treatment increased RGS2 mRNA and protein expression. PGE 2 treatment of MSM cells also significantly attenuated G αq ‐coupled GPCR‐stimulated calcium flux response to subsequent treatment with maximally effective concentrations of either oxytocin or histamine. This effect was mimicked by adenoviral overexpression of RGS2, supporting the hypothesis that repression of contraction can be caused by RGS2. Knockdown of PGE2‐induced RGS2 with siRNA in MSM cells is underway to confirm whether RGS2 is indeed responsible for the attenuation of histamine and oxytocin calcium signals that is observed in cells pre‐treated with PGE 2. Conclusion These findings support a pro‐quiescent role of PGE 2 , in part by the protective function of RGS2 attenuating some G αq ‐protein coupled receptor contractile signals. Further investigation is underway to establish to what extent the other aspects of G αq ‐protein coupled receptor signaling that contribute to labour may also be attenuated by RGS2 signals. Support or Funding Information This work is supported by the Canadian Institues for Health Research (CIHR), and DU is funded by an Alberta Innovates Health Solutions (AIHS) MD‐PhD Studentship. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
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 | 0,001 | 0,000 |
| Communication savante | 0,000 | 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) | 0,000 | 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 ».