In vitro study | Using 1μM TWS119 to treat P19 cells, 30-40% of the cells were differentiated, especially into nerve cell spectrum, according to the correct neuron morphology (by standard EB formation method, accompanied by TWS119 treatment, produce 60% neural differentiation) count TuJ1 positive cells. TWS119 binds tightly to GSK-3β(K D = 126 nM), quantified by surface plasmon resonance (SPR), with an IC50 of 30 nM. TWS119 acts on mouse embryonic carcinoma and ES cells and effectively induces neural differentiation. TWS119 treatment of hepatic stellate cells (HSC) reduced β-catenin phosphorylation, Induced β-catenin nuclear translocation, increased glutamine synthetase production, hindered the synthesis of smooth muscle actin and Wnt5a, but promoted glial protein acidic protein, expression of Wnt10b, and paired homeodomain transcription factor 2c. TWS119 triggers the rapid accumulation of β-catenin, enhances the nuclear protein interaction with oligonucleotides (DNA sequences containing Tcf and Lef binding), and greatly up-regulates Tcf7, Lef1 and other Wnt target genes including Jun, ezd7 (encoding Frizzled-7), Nlk (encoding Nemo-like kinase). TWS119 increases T-cell specific lethality and IFN-g release associated with protective IL-2 production capacity. Recent studies have shown that TWS119 treatment polyclonal activates human T cells and induces Wnt signaling. These T cells have the native CD45RA(+)CD62L(+) phenotype compared to control activated T cells expressing the CD45RO(+)CD62L(-) effector phenotype, this effect was TWS119 dose-dependent. |