Exogenous bone morphogenetic protein-7 reduces hepatic fibrosis in Schistosoma japonicum-infected mice via transforming growth factor-β/Smad signaling.

AIM: To investigate the antifibrotic effects of bone morphogenetic protein-7 (BMP-7) on Schistosoma japonicum (S. japonicum)-induced hepatic fibrosis in BALB/C mice. METHODS: Sixty BALB/C mice were randomly divided into three groups, including a control group (group A, n = 20), model group (group B, n = 20) and BMP-7 treated group (group C, n = 20). The mice in group B and group C were abdominally infected with S. japonicum cercariae to induce a schistosomal hepatic fibrosis model. The mice in group C were administered human recombinant BMP-7. Liver samples were extracted from mice sacrificed at 9 and 15 wk after modeling. Hepatic histopathological changes were assessed using Masson's staining. Transforming growth factor-beta 1 (TGF-beta 1), alpha-smooth muscle actin (alpha-SMA), phosphorylated Smad2/3 (pSmad2/3) and Smad7 protein levels and localization were measured by Western blotting and immunohistochemistry, respectively, and their mRNA expressions were detected by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: The schistosomal hepatic fibrosis mouse model was successfully established, as the livers of mice in group B and group C showed varying degrees of typical schistosomal hepatopathologic changes such as egg granuloma and collagen deposition. The degree of collagen deposition in group C was higher than that in group A (week 9: 22.95 +/- 6.66 vs 2.02 +/- 0.76; week 15: 12.84 +/- 4.36 vs 1.74 +/- 0.80; P < 0.05), but significantly lower than that in group B (week 9: 22.95 +/- 6.66 vs 34.43 +/- 6.96; week 15: 12.84 +/- 4.36 vs 18.90 +/- 5.07; P < 0.05) at both time points. According to immunohistochemistry data, the expressions of alpha-SMA, TGF-beta 1 and pSmad2/3 protein in group C were higher than those in group A (alpha-SMA: week 9: 21.24 +/- 5.73 vs 0.33 +/- 0.20; week 15: 12.42 +/- 4.88 vs 0.34 +/- 0.27; TGF-beta 1: week 9: 37.00 +/- 13.74 vs 3.73 +/- 2.14; week 15: 16.71 +/- 9.80 vs 3.08 +/- 2.35; pSmad2/3: week 9: 12.92 +/- 4.81 vs 0.83 +/- 0.48; week 15: 7.87 +/- 4.09 vs 0.90 +/- 0.45; P < 0.05), but significantly lower than those in group B (alpha-SMA: week 9: 21.24 +/- 5.73 vs 34.39 +/- 5.74; week 15: 12.42 +/- 4.88 vs 25.90 +/- 7.01; TGF-beta 1: week 9: 37.00 +/- 13.74 vs 55.66 +/- 14.88; week 15: 16.71 +/- 9.80 vs 37.10 +/- 12.51; pSmad2/3: week 9: 12.92 +/- 4.81 vs 19.41 +/- 6.87; week 15: 7.87 +/- 4.09 vs 13.00 +/- 4.98; P < 0.05) at both time points; the expression of Smad7 protein in group B was higher than that in group A and group C at week 9 (8.46 +/- 3.95 vs 1.00 +/- 0.40 and 8.46 +/- 3.95 vs 0.77 +/- 0.42; P < 0.05), while there were no differences in Smad7 expression between the three groups at week 15 (1.09 +/- 0.38 vs 0.97 +/- 0.42 vs 0.89 +/- 0.39; P > 0.05). Although minor discrepancies were observed, the results of RT-PCR and Western blotting were mainly consistent with the immunohistochemical results. CONCLUSION: Exogenous BMP-7 significantly decreased the degree of hepatic fibrosis in both the acute and chronic stages of hepato-schistosomiasis, and the regulatory mechanism may involve the TGF-beta/Smad signaling pathway. (C) 2013 Baishideng. All rights reserved.