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.