Increased fibronectin (FN) expression has an important role during liver fibrosis. The present study examined FN expression in rats subjected to carbon tetrachloride (CCl4)-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 CCl4. Furthermore, HSC-T6 cells were stimulated with increasing doses of recombinant TGF-β over 24 h. Hepatic fibrosis gradually increased following CCl4 administration in vivo. Western blotting and immunohistochemistry demonstrated that fibronectin (FN), TGF-β and α-smooth muscle actin (SMA) expression was increased following CCl4 injection, and the maximum expression levels were observed at 8 weeks. Once CCl4 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.

Aim: To evaluate the antifibrotic effect of telmisartan, an angiotensin II receptor blocker, in bile duct-ligated rats. Methods: Adult Sprague-Dawley rats were allocated to 3 groups: sham-operated rats, model rats underwent common bile duct ligation (BDL), and BDL rats treated with telmisartan (8 mg/kg, po, for 4 weeks). The animals were sacrificed on d 29, and liver histology was examined, the Knodell and Ishak scores were assigned, and the expression of angiotensin-converting enzyme (ACE) and ACE2 was evaluated with immunohistochemical staining. The mRNAs and proteins associated with liver fibrosis were evaluated using RTQ-PCR and Western blot, respectively. Results: The mean fibrosis score of BDL rats treated with telmisartan was significantly lower than that of the model rats (1.66±0.87 vs 2.13±0.35, P=0.015). However, there was no significant difference in inflammation between the two groups, both of which showed moderate inflammation. Histologically, treatment with telmisartan significantly ameliorated BDL-caused the hepatic fibrosis. Treatment with telmisartan significantly upregulated the mRNA levels of ACE2 and MAS, and decreased the mRNA levels of ACE, angiotensin II type 1 receptor (AT1-R), collagen type III, and transforming growth factor β1 (TGF-β1). Moreover, treatment with telmisartan significantly increased the expression levels of ACE2 and MAS proteins, and inhibited the expression levels of ACE and AT1-R protein. Conclusion:Telmisartan attenuates liver fibrosis in bile duct-ligated rats via increasing ACE2 expression level.

The results suggest that PGG may be responsible for the antifungal activity of PRB by disrupting the structure of cell wall directly.