Stay Connected. Manage Your Care.
Access your health information anytime and anywhere, at home or on the go, with MyHealth.
- Message your clinic
- View your lab results
- Schedule your next appointment
- Pay your bill
The MyHealth mobile app from Stanford Health Care puts all your health information at your fingertips and makes managing your health care simple and quick.
Guest Services
24/7
We are available to assist you
whenever you need it. Give us a call at
650-498-3333 or
PHYSICIAN HELPLINE
Have a question? We're here to help! Call 1-866-742-4811
Monday - Friday, 8 a.m. - 5 p.m.
REFER A PATIENT
Fax 650-320-9443
Track your patients' progress and communicate with Stanford providers conveniently and securely.
Abstract
Numerous liver diseases are associated with extensive oxidative tissue damage. It is well established that Wnt/β-catenin signaling directs multiple hepatocellular processes including development, proliferation, regeneration, nutrient homeostasis and carcinogenesis. It remains un-explored whether Wnt/β-catenin signaling provides hepatocyte protection against hepatotoxin-induced apoptosis. Conditional, liver-specific β-catenin knockdown (KD) mice and their wild-type littermates were challenged by feeding the hepatotoxin 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet to induce chronic oxidative liver injury. Following DDC diet, mice with β-catenin-deficient hepatocytes demonstrate increased liver injury, indicating an important role of β-catenin signaling for liver protection against oxidative stress. This finding was further confirmed in AML12 hepatocytes with β-catenin signaling manipulation in vitro using paraquat, a known oxidative stress inducer. Immunofluorescence staining revealed an intense nuclear FoxO3 staining in β-catenin-deficient livers, suggesting active FoxO3 signaling in response to DDC-induced liver injury when compared to wild-type controls. Consistently, FoxO3 target genes p27 and Bim were significantly induced in β-Catenin KD livers. Conversely, SGK1, a β-catenin target gene, was significantly impaired in β-catenin KD hepatocytes that failed to inactivate FoxO3. Furthermore, shRNA mediated deletion of FoxO3 increased hepatocyte resistance to oxidative stress-induced apoptosis, confirming a pro-apoptotic role of FoxO3 in the stressed liver. Our findings suggest that Wnt/β-catenin signaling is required for hepatocyte protection against oxidative stress-induced apoptosis. The inhibition of FoxO through its phosphorylation by β-catenin induced SGK1 expression reduces FoxO3`s apoptotic function, resulting in increased hepatocyte survival. These findings have relevance for future therapies directed at hepatocyte protection, regeneration and anti-cancer treatment.
View details for DOI 10.1074/jbc.M112.445965
View details for Web of Science ID 000320380600018
View details for PubMedID 23620592