Disclosures: The following people have nothing to disclose: Sarah Bligh, Kusum K. Khar-banda, Paul G. Thomes The alcoholic liver disease (ALD) patients develop fatty liver, chronic hepatitis, and even hepatic fibrosis or cirrhosis. However,

selleck screening library the underlying mechanism in which alcohol consumption causes ALD progression remains elusive. Pro-inflammatory cytokines induced apoptosis has been suggested in ALD progression. Wnt/β-catenin signaling recently has been shown to involve in inflammation and apoptosis, suggesting that Wnt/β-catenin might modulate ALD progression. The current study is proposed to determine whether activation of Wnt/β-catenin signaling could attenuate ALD progression. Chronic ALD rat model exhibited an induced apoptosis mediated by FOXO3a accompany with reduced Wnt/β-catenin https://www.selleckchem.com/products/Imatinib-Mesylate.html signaling in the livers of alcohol-fed rats. Using molecular mutation strategy, FOXO3a without DNA binding domain could not enhance the expression of BIM, a FOXO3a induced apoptotic gene, in human hepatocytes implying that FOXO3a is critical in modulating apoptosis in hepatocytes. Activation of Wnt/β-catenin signaling suppressed FOXO3a-induced apoptosis via up-regulation of serum/glucocorticoid regulated kinase 1 (SGK1). Moreover, pre-treatment of human hepatocytes with SGK1 inhibitor reversed the inhibition of FOXO3a expression, suggesting that SGK1 is

essential in FOXO3a-induced apoptosis modulated by Wnt/β-catenin signaling. Pharmacological restoration

of Wnt/ p-catenin signaling shows decreased steatosis and reduced alanine aminotransferase enzymatic activities in the livers of alcohol-fed rats. Consistent with in vitro data, activation of Wnt/β-catenin signaling suppresses FOXO3a and cleaved caspase 3 in vivo, indicating that activation of Wnt/β-catenin signaling attenuates ALD progression through inhibiting apop-tosis. Conclusion: Wnt/β-catenin signaling plays a protective role in ALD progression via antagonizing however FOXO3a-induced apoptosis and pharmacological activation of Wnt/β-catenin might be a potential therapy in ALD. Disclosures: The following people have nothing to disclose: Chiung-Kuei Huang, Tunan Yu, Zoltan Derdak, Suzanne M. de la Monte, Jack R. Wands, Miran Kim Background: Claudin-2 is an epithelial cell tight junction protein expressed in intestine, liver, kidneys and pancreas, and is up-regulated by inflammation. A high-risk locus encompassing the claudin-2 gene (CLDN2) on the X chromosome was strongly associated with chronic pancreatitis (CP, p<10e-21), especially with alcohol, on a GWAS. Chronic liver disease (CLD) and CP share risk factors for development such as alcohol and smoking, and occur concurrently in some patients while others develop one or other chronic fibrotic disease. Factors that determine which disease develops in an individual are not well known.