Original Article
Copyright ©2013 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Mar 7, 2013; 19(9): 1405-1415
Published online Mar 7, 2013. doi: 10.3748/wjg.v19.i9.1405
Exogenous bone morphogenetic protein-7 reduces hepatic fibrosis in Schistosoma japonicum-infected mice via transforming growth factor-β/Smad signaling
Bo-Lin Chen, Jie Peng, Qing-Fu Li, Min Yang, Yuan Wang, Wei Chen
Bo-Lin Chen, Jie Peng, Qing-Fu Li, Yuan Wang, Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
Min Yang, Department of Respiration, Hunan Children’s Hospital, Changsha 410011, Hunan Province, China
Wei Chen, Department of Gastroenterology, Changsha Central Hospital, Changsha 410004, Hunan Province, China
Author contributions: Chen BL designed the research, performed the majority of the experiments and wrote the manuscript; Peng J supervised the research; Yang M was involved in revising the manuscript; Li QF, Wang Y and Chen W helped perform the research and participated in data analysis.
Correspondence to: Dr. Jie Peng, Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China. pengjie2@medmail.com.cn
Telephone: +86-731-84327321 Fax: +86-731-84327321
Received: August 11, 2012
Revised: January 14, 2013
Accepted: January 23, 2013
Published online: March 7, 2013
Processing time: 151 Days and 23.1 Hours
Abstract

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-β1), alpha-smooth muscle actin (α-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 α-SMA, TGF-β1 and pSmad2/3 protein in group C were higher than those in group A (α-SMA: week 9: 21.24 ± 5.73 vs 0.33 ± 0.20; week 15: 12.42 ± 4.88 vs 0.34 ± 0.27; TGF-β1: 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 (α-SMA: week 9: 21.24 ± 5.73 vs 34.39 ± 5.74; week 15: 12.42 ± 4.88 vs 25.90 ± 7.01; TGF-β1: 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-β/Smad signaling pathway.

Keywords: Bone morphogenetic protein-7; Schistosoma japonicum; Hepatic fibrosis; Smad; BALB/C mice