التفاصيل البيبلوغرافية
| العنوان: |
Absence of beta‐catenin in liver attenuates bile duct injury |
| المؤلفون: |
Nejak‐Bowen, Kari Nichole, Thompson, Michael D, Monga, Satdarshan P |
| المساهمون: |
National Institutes of Health |
| المصدر: |
The FASEB Journal ; volume 27, issue S1 ; ISSN 0892-6638 1530-6860 |
| بيانات النشر: |
Wiley |
| سنة النشر: |
2013 |
| المجموعة: |
Wiley Online Library (Open Access Articles via Crossref) |
| الوصف: |
While the pathology of biliary fibrosis is well described, the signaling pathways involved in the proliferation and activity of the cholangiocyte compartment during cholestatic liver injury are incompletely understood. β‐Catenin, the chief downstream effector of the Wnt signaling pathway, has been shown to play an important role during bile duct development but its role in adult bile duct homeostasis remains undetermined. Hepatocyte and cholangiocyte‐specific β‐catenin knockout (KO) when fed a diet containing 0.1% 3,5‐diethoxycarbonyl‐1,4‐dihydrocollidine (DDC) for 1–2 weeks showed decreased atypical ductular reaction as compared to wildtype littermates (WT). KO and WT were next subjected to bile duct ligation (BDL), which led to an increase in bilirubin in both WT and KO mice after 14 days. However, levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, and gamma glutamyl transpeptidase (GGTP) were significantly lower in KO when compared to WT. This was associated with a dramatic decrease in ductular reaction and fibrosis in β‐catenin KO livers. Further analysis yielded a notable decrease in total hepatic bile acids (BA) in the KO, which was associated with an increased FXR/SHP2 activation. This led to reduced BA synthesis and increased excretion. Thus, loss of β‐ catenin limits cholestatic injury in multiple models by modulating BA biosynthesis. These findings support an important role of Wnt/β‐catenin signaling in bile duct homeostasis and repair. This study was funded b y NIH grant 1R01DK62277 to SPM. |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
English |
| DOI: |
10.1096/fasebj.27.1_supplement.387.3 |
| الإتاحة: |
https://doi.org/10.1096/fasebj.27.1_supplement.387.3Test |
| حقوق: |
http://onlinelibrary.wiley.com/termsAndConditions#vorTest |
| رقم الانضمام: |
edsbas.D1120FEC |
| قاعدة البيانات: |
BASE |
