HNF1/Tcf1 may represent one point of convergence within this regulatory network as the levels of expression induced by BMP-4 are higher in wild-type cells than in the Hex−/− endoderm and dramatically enhanced by the enforced expression of Hex. In addition to playing a regulatory role at the level of Tcf1 expression, evidence exists that Hex can physically interact with Tcf132 suggesting that these transcription factors may function as coactivators of downstream targets. In conclusion, the findings presented here document a pivotal role for Hex in the establishment of the hepatic lineage in ESC cultures

and in doing so provide further evidence that lineage

commitment Selleck Poziotinib in this model accurately reflects that observed in the early embryo. Stage-specific enforced expression of Hex promoted hepatic development and maturation, indicating that this strategy may provide an efficient method find more for the production of relatively mature cell types for studies on lineage commitment, for transplantation in preclinical model of liver disease and for drug discovery and analyses. We thank Mako Yabunouchi and Fumie Otsuka for their excellent technical assistance. Additional Supporting Information may be found in the online version of this article. “
“Aim:  To evaluate the role of natural killer (NK)T cells in the pathogenesis of non-alcoholic steatohepatitis (NASH), here we investigated the expression and function of hepatic NKT cells in KK-Ay mice, an animal model of metabolic syndrome. Methods:  Male, 8-week-old KK-Ay and C57Bl/6 mice were fed a high-fat (HF) diet for 4 weeks. Some mice were given daily intragastric injections of pioglitazone for 5 days prior to or after dietary treatment. Results:  In untreated KK-Ay mice, the percentages of NKT cells in liver mononucleolar cells were

nearly one-third of those in C57Bl/6 controls. Elevations in interleukin (IL)-4 and interferon (IFN)-γ mRNA in the liver after a single injection of α-galactosylceramide Montelukast Sodium (GalCer) were blunted in KK-Ay mice largely. Percentages of NKT cells, as well as GalCer-induced increases in IL-4 mRNA, were blunted significantly in both strains after HF diet feeding for 4 weeks. Interestingly, KK-Ay mice pretreated with pioglitazone showed significant increases in NKT cell proportion, and GalCer-induced increases in IL-4 and IFN-γ mRNA were also enhanced by pioglitazone. In KK-Ay mice, the percentages of annexin V positive NKT cells were nearly 2.5-fold higher than those in C57Bl/6 controls; however, pioglitazone decreased annexin V positive cells significantly. Moreover, pioglitazone increased NKT cell fraction in KK-Ay mice even after HF diet feeding.