Effect of TNF-like weak inducer of apoptosis and its receptor on migration of hepatic stellate cells

Objective To investigate the effect of TNF-like weak inducer of apoptosis (TWAEK) and its receptor fibroblast growth factor-inducible 14 (Fn14) on the migration of hepatic stellate cells and the possible mechanism. Methods The human hepatic stellate cell line LX-2 cells were treated with TWEAK or Fn14 specific small interfering RNA (Fn14 siRNA)+TWEAK. Transwell chamber was used to observe the migration of hepatic stellate cells, and real-time PCR and Western blot were used to measure the expression of matrix metalloproteinase-9 (MMP9). The independent samples t-test was used for comparison of continuous data between two groups; a one-way analysis of variance was used for comparison between multiple groups, and the least significant difference t-test was used for further comparison between two groups. Results Compared with normal LX-2 cells, the TWEAK group had a significant increase in the migration of LX-2 cells (105±8 vs 164±17, t=5.287,P＜0.01), and compared with the negative control group, the Fn14 siRNA+TWEAK group had a significant reduction in the number of migrated cells (122±9 vs 58±7, t=9.836, P＜0.01). When LX-2 cells were treated with TWEAK, the mRNA and protein expression of MMP9 increased in a time-dependent manner (both P＜0.05), while the Fn14 siRNA+TWEAK group had significant reductions in the mRNA and protein expression of MMP9 compared with the TWEAK group (t=5.358, P＜0.01). Conclusion TWEAK and its receptor Fn14 can promote the migration of hepatic stellate cells by upregulating MMP9, and blockade of this pathway may become a potential target for the treatment of liver fibrosis