Thymosin β4 attenuates liver fibrosis via suppressing Notch signaling

Thymosin β4 (Tβ4) has been shown to have beneficial effects in a number of pathological processes. Although there was research reporting the endogenous expression of Tβ4 influences hepatic stellate cells (HSCs) activation, the effect of exogenous administration of Tβ4 in hepatic fibrosis remains unclear. In the current study, we used CCl₄-induced liver fibrosis model mice to investigate the effect of Tβ4 administration on fibrosis in vivo and the underlying mechanism. Our study indicates that Tβ4 attenuates hepatic fibrosis and down-regulates the expression of fibrogenic genes in hepatic liver. In addition, Tβ4 inhibits the expression of pro fibrogenic and proliferation genes in activated HSCs. Further study revealed that Tβ4 attenuates liver fibrosis through inhibition of the Notch signaling, as Tβ4 significantly reduces the expression of Notch2 and Notch 3 that were increased in hepatic liver. Our data indicate that Tβ4 might be an effective anti-fibrotic drug for the treatment of liver fibrosis.