التفاصيل البيبلوغرافية
| العنوان: |
β‐catenin knockout mice are protected from TNF‐α mediated apoptosis |
| المؤلفون: |
Nejak‐Bowen, Kari Nichole, Tan, Xinping, Monga, Satdarshan |
| المصدر: |
The FASEB Journal ; volume 24, issue S1 ; ISSN 0892-6638 1530-6860 |
| بيانات النشر: |
Wiley |
| سنة النشر: |
2010 |
| المجموعة: |
Wiley Online Library (Open Access Articles via Crossref) |
| الوصف: |
β‐catenin plays multiple roles in liver health and disease through regulation of processes such as proliferation, differentiation and adhesion. However its role in hepatic injury remains unexplored. Here, we demonstrate that loss of β‐catenin protects against TNF‐α mediated apoptosis. Analysis of mRNA expression levels in wild‐type (WT) and β‐catenin knockout (KO) mice reveals that KO livers have an increased expression of TNF‐α induced genes, as determined by gene array. Additionally, baseline levels of caspase‐3 and caspase‐8 are increased in KOs over WTs. WT and KO mice injected with either galactosamine (GalN) or actinomycin D (ActD) and lipopolysaccharide (LPS) (which activates the TNF‐α pathway) were monitored for morbidity. Surprisingly, KO mice are refractory to both GalN/LPS and ActD/LPS treatment: the mice show decreased morbidity, and examination of WT and KO livers morphologically and histologically upon sacrifice reveals that KO mice are protected from damage and apoptosis. Analysis of liver enzymes and TUNEL staining confirms the presence of massive injury and apoptosis in WT but not in KO mice. Expression of NF‐κB p50 and p65, as well as their downstream targets Fas and Traf‐1, are unchanged between WT and KO under unstimulated conditions. However, levels of the anti‐apoptotic transcription factors GSK‐3β and NF‐κB are elevated in KO mice as compared to WT after insult. In conclusion, our results demonstrate that deletion of β‐catenin from hepatocytes confers protection from TNF‐α induced injury and apoptosis, perhaps through a compensatory upregulation of the anti‐apoptotic NF‐κB pathway. |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
English |
| DOI: |
10.1096/fasebj.24.1_supplement.38.5 |
| الإتاحة: |
https://doi.org/10.1096/fasebj.24.1_supplement.38.5Test |
| حقوق: |
http://onlinelibrary.wiley.com/termsAndConditions#vorTest |
| رقم الانضمام: |
edsbas.14318BEC |
| قاعدة البيانات: |
BASE |
