[Results] Of 27,342 genes examined, 181 genes are commonly suppressed with all three inhibitors. Two of the genes conspicuously repressed are Scd1 and Scd2. Scd1/2 inductions are associated with increased desaturation index of fatty acids in cultured aHSCs and are also confirmed in HSCs isolated from CCl4-induced AZD1208 concentration and cholestatic rat liver fibrosis. Cre-mediated ablation of Scd1f/f or Scd2f/f in

HSCs or A939572 treatment in culture, de-represses the HSC differentiation gene Pparγ and reverses morphologic and biochemical features of HSC activation. These effects are rescued with OA or POA, the SCD products but not with their precursors, stea-rate and palmitate. CTNNB1 is enriched at the Scd1 proximal promoter site containing classical SRE and NF-Y element, and re-ChIP confirms CTNNB1 association with SREBP-1c bound to the site. CTNNB1 enhances ∼10 fold SREBP-1c mediated Scd1 transcription, demonstrating CTNNB1 is a potent

co-activator for the gene. SCD inhibition reduces integrin-linked see more kinase (ILK) activity, p(S9)-GSK3β and p-AKT, and CTNNB1 stabilization. Inhibition of ILK phenocopies the effects of SCD inhibition, however the latter but not the former effects are rescued with OA, suggesting ILK is downstream of SCD. SCD inhibition with A939572 or conditional knockout of Scd2 in aHSCs in Col1a1-Cre:Scd2f/f mice attenuates CCl4-induced liver αSMA accumulation and fibrosis. [Conclusion] WNT/CTNNB1-in-duced SCD positively feeds back to activate CTNNB1 and HSCs via ILK and is a new potential therapeutic target for liver fibrosis. Disclosures: Hidekazu Tsukamoto – Consulting:

Shionogi & Co., S.P. Pharmaceutics; Grant/ Research Support: The Toray Co. The following people have nothing to disclose: Soo-Mi Kweon, Keane Lai, Lan Qin, Jun Xu, Naoki Fujii, Samuel W. French, James Ntambi Introduction: Liver microenvironment is a critical determinant for development and progression of liver metastasis. Under TGF-β stimulation, hepatic stellate cells (HSCs), which are liver specific pericytes, transdifferentiate into many myofibroblasts that promote tumor implantation and growth in the liver. The regulation of this HSC activation process in the liver however remains poorly understood. In this study, we tested if actin binding protein vasodilator-stimulated phosphoprotein (VASP) regulated TGF-β mediated HSC activation and tumor growth in mice. Methods: VASP expression in tumor activated HSCs was investigated by immunofluorescence staining (IF) on liver biopsies of mice and patients. The role of stellate cell VASP in tumor growth was studied in a HSC/tumor coimplantation mouse model. VASP shRNA and siRNA were used to knockdown VASP in primary human HSCs and LX2 cells. TGF-β activation of HSCs was quantitated by IF for alpha- smooth muscle actin (α-SMA) and Western blot analysis (WB).