Fibronectin expression is critical for liver fibrogenesis in vivo and in vitro

Increased fibronectin (FN) expression has an important role during liver fibrosis. The present study examined FN expression in rats subjected to carbon tetrachloride (CCl(4))-induced liver fibrosis. In addition, the potential mechanisms underlying fibrogenesis were investigated by exposing hepatic stellate cells (HSCs) to transforming growth factor-β (TGF-β), which is a known inducer of myofibroblastic transformation of HSCs. Briefly, a rat model of liver fibrosis was created by administering intraperitoneal injections of CCl(4). Furthermore, HSC-T6 cells were stimulated with increasing doses of recombinant TGF-β over 24 h. Hepatic fibrosis gradually increased following CCl(4) administration in vivo. Western blotting and immunohistochemistry demonstrated that fibronectin (FN), TGF-β and α-smooth muscle actin (SMA) expression was increased following CCl(4) injection, and the maximum expression levels were observed at 8 weeks. Once CCl(4) treatment had been terminated, the expression levels of FN, TGF-β and α-SMA progressively declined to near baseline levels. Western blotting and quantitative polymerase chain reaction demonstrated that FN expression was gradually increased in response to TGF-β-stimulation of HSCs; maximum expression was achieved 12 h post-treatment (P<0.01 vs. the baseline). In conclusion, these findings indicated that FN expression is an early and progressive event that occurs during liver fibrogenesis in vivo and in vitro.