Poster Session 2: Donor and Allocation Issues: Living Donor and Split Liver Transplantation and Hepatobiliary Surgery; Experimental Steatohepatitis
Notice bibliographique
Résumé
Cholestatic liver diseases are characterized by increased biliary proliferation and intrahepatic bile duct mass (IBDM), liver damage and fibrosis. Melatonin, which is synthesized in the pineal gland as well as cholangiocytes, exerts its effects by interaction with MT1 and MT2 receptors. Knockdown of MT2 increases biliary proliferation and liver fibrosis in cholestatic mice. Also, melatonin inhibits biliary hyperplasia by interacting with MT1 receptors. However, since these studies were performed only in vitro, we evaluated the role of MT1 in regulating biliary proliferation and liver fibrosis in vivo in MT1 knockout (KO) mice, and wild-type (WT) mice in which the hepatic expression of MT1 was reduced by Vivo-Morpholinos for MT1. Methods: The studies were performed in normal (WT), MT1 Morpholino-treated or MT1 KO mice with or without BDL surgery. We evaluated the expression of MT1 in liver sections by immunohistochemistry (IHC) and immunoblots in cholangiocytes. Intrahepatic biliary ductal mass (IBDM) and biliary proliferation was evaluated by IHC for CK-19 and PCNA in liver sections, and qPCR for PCNA in cholangiocytes. Liver injury was determined by H&E staining in liver sections and serum levels of transaminases and bilirubin. Fibrosis was evaluated by Sirius red staining in liver sections and qPCR for TGFbeta1, alpha-SMA and fibronectin in cholangiocytes and total liver. In vitro, shRNA-MT1 transfected murine cholangiocytes (MCCs) and controls were used to measure proliferation and TGFbeta1, alpha-SMA and fibronectin (FN-1) mRNA expression by qPCR. Results: Normal cholangiocytes express low levels of MT1, which markedly increased after BDL. We demonstrated that in MT1 KO BDL and MT1 Morpholino-treated BDL mice, along with reduced MT1 expression, there was decreased biliary proliferation and IBDM. In MT1 KO BDL and MT1 Morpholino-treated BDL mice, there was decreased lobular damage, serum levels of transaminases and bilirubin, and liver fibrosis in liver sections and reduced expression of TGFbeta1, alpha-SMA and FN-1 compared to BDL WT mice. In shRNA-MT1 transfected MCCs, there was decreased proliferation and reduced expression of TGFb1, alpha-SMA and FN-1. The findings indicate that shifting the melatonin axis to signal via MT2 during the knockdown of MT1 expression decreases biliary proliferation and liver fibrosis. Conclusion: Our findings indicate that the balance of MT1/MT2 receptor expression for the melatonin signaling axis may play an important role in the regulation of biliary proliferation and hepatic fibrosis. Inhibition of MT1 may be a key approach for ameliorating biliary hyperplasia and liver fibrosis in cholestatic liver diseases.
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) | 0,000 | 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 ».