TWEAK increases SIRT1 expression and promotes p53 deacetylation affecting human hepatic stellate cell senescence.

To detect the effects of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) on SIRT1 expression and p53 deacetylation, involving cell senescence, in activated human hepatic stellate cell (HSC) in vitro, human HSC LX-2 was cultured with TWEAK for 24 h. The result showed that the expression of membrane receptor Fn14 was remarkably increased by TWEAK, which upregulated SIRT1 in LX-2 cells, detected by Western blotting and real-time PCR. The expression of p53 was not significantly altered; however, the ac-p53 was decreased. Furthermore, the viability of LX-2 cells was significantly enhanced by TWEAK. The activity of SA-β-Gal was notably inhibited, showing a suppressing effect of TWEAK on the senescence of activated HSC. Primary cultured HSC on days 7 and 11 was used to examine the expression of TWEAK, Fn14, SIRT1, and the activity of SA-β-Gal. The result indicated that the mRNA of TWEAK, SIRT1, and Fn14 was all decreased on day 11 compared to that on day 7, and the activity of SA-β-Gal was higher on day 11 than that on day 7. The present study suggested that TWEAK enhanced the expression of SIRT1 and decreased the acetylation of p53, probably inhibiting the senescence of activated HSC in vitro, which provides a molecular basis for TWEAK as a potential target in the therapy of liver fibrosis.