87. Angiotensin II Type 2 Receptor Signal Modulation in Models of Cutaneous Wound Healing
Notice bibliographique
Résumé
PURPOSE: Globally, hypertrophic scarring remains a major burden for patients, resulting in significant aesthetic and functional morbidity. A variety of methods that target cellular pathways during wound healing have been proposed to reduce skin scarring. One candidate target is the angiotensin II type 2 receptor (AT2R), whose signaling has been shown to be antifibrotic. Compound 21 (C21) is a selective AT2R agonist previously shown in vitro and in vivo to reduce cardiac and renal fibrosis by limiting myofibroblast activity and collagen production. We sought to modulate AT2R signaling using C21 and the AT2R antagonist, PD123319, in models of cutaneous wound healing to determine whether this pathway can be exploited to reduce scarring. METHODS: A splinted wound model was employed in mice to recapitulate early phases of the tethered-skin wound healing observed in humans. Ten-week-old male Balb/c mice received two, full-thickness dorsal skin wounds that were splinted with silicone rings and covered with a semipermeable membrane. On alternating days, one wound received topical 20uM C21 (n=12) or PD123319 (10uM; n=8), while the other received saline vehicle, until sacrifice on day 10. Wounds, including surrounding healthy skin, were then harvested for histology and qPCR analyses. Scratch assays were performed on human dermal fibroblasts and keratinocytes to assess C21 and PD123319 activity in vitro. RESULTS: C21 treatment did not affect the rate of reepithelialisation, while PD123319 treatment accelerated wound closure (p=0.03 vs saline). Collagen density was increased in C21-treated wounds (p=0.01 vs saline), similar to normal unwounded skin, but was decreased with PD123319 treatment (p=0.04 vs saline and 0.0001 vs C21). C21 also increased vascular density relative to saline (p=0.01). We observed upregulation of genes associated with regeneration and repair including Col6a1 (p=0.007), NGF (p=0.012), and mast cell markers Ms4a2 (p=0.001) and Tpsb2 (p=0.009) with C21 treatment, while PD123319 treatment reduced Col1a1 gene expression (p=0.047). C21-treated wounds had a marked reduction in immune cell infiltration compared to PD123319 and saline-treated wounds and more closely resembled normal skin. Similarly, 50uM C21 reduced both fibroblast (p<0.0001 vs vehicle) and keratinocyte (p=0.004 vs PD123319) migration via scratch assay in vitro. CONCLUSION: In our early wound healing model, AT2R activation was associated with collagen density comparable to that of unwounded skin and increased vascular density. Inhibition of AT2R led to rapid re-epithelialization and reduced collagen deposition consistent with atrophic wounds. We are also addressing the possibility of a mast cell-related mechanism with future experiments. AT2R signal modulation is, therefore, a potential therapeutic target to improve skin quality during wound healing.
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 | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,001 |
| 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 ».