Abstract
BackgroundLiver fibrosis is a hallmark of clonorchiasis suffered by millions people in Eastern Asian countries. Recent studies showed that the activation of TGF-β/Smad signaling pathway can potently regulate the hepatic fibrogenesis including Schistosoma spp. and Echinococcus multilocularis-caused liver fibrosis. However, little is known to date about the expression of transforming growth factor-β (TGF-β) and other molecules in TGF-β/Smad signaling pathway which may play an important role in hepatic fibrosis caused by C. sinensis.MethodsA total of 24 mice were individually infected orally with 45 metacercariae, both experimental mice and mocked-infected control mice were anesthetized at 4 week post-infection (wk p.i.), 8 wk p.i. and 16 wk p.i., respectively. For each time-point, the liver and serum from each animal were collected to analyze histological findings and various fibrotic parameters including TGF-β1, TGF-β receptors and down-stream Smads activation, as well as fibrosis markers expression.ResultsThe results showed that collagen deposition indicated by hydroxyproline content and Masson’s trichrome staining was increased gradually with the development of infection. The expression of collagen type α1 (Col1a) mRNA transcripts was steadily increased during the whole infection. The mRNA levels of Smad2, Smad3 as well as the protein of Smad3 in the liver of C. sinensis-infected mice were increased after 4 wk p.i. (P < 0.05, compared with normal control) whereas the TGF-β1, TGF-β type I receptor (TGFβRI) and TGF-β type II receptor (TGFβRII) mRNA expression in C. sinensis-infected mice were higher than those of normal control mice after 8 wk p.i. (P < 0.05). However, the gene expression of Smad4 and Smad7 were peaked at 4 wk p.i. (P < 0.05), and thereafter dropped to the basal level at 8 wk p.i., and 16 wk p.i., respectively. The concentrations of TGF-β1 in serum in the C. sinensis-infected mice at 8 wk p.i. and 16 wk p.i (P < 0.05) were significantly higher than those in the control mice.ConclusionsThe results of the present study indicated for the first time that the activation of TGF-β/Smad signaling pathway might contribute to the synthesis of collagen type I which leads to liver fibrosis caused by C. sinensis.
Highlights
Liver fibrosis is a hallmark of clonorchiasis suffered by millions people in Eastern Asian countries
In the C. sinensis-infected group, fibrotic cords were observed in the periportal areas of C. sinensis- infected mice at 4 wk p.i. and 8 wk p.i., and as the infection developed, collagen fibers were extended from portal areas to liver lobule of mice at 16 wk p.i., the arrangement of hepatocyte was disordered and pseudolobules were observed in some serious cases at this time point (Figure 1A and Figure 1B)
The results showed that mRNA levels of collagen α1 (Col1a) expression were steadily increased from 4 wk p.i. to 16 wk p.i., and significant differences were found at 8 wk p.i. (P < 0.05) and 16 wk p.i. (P < 0.05), compared with normal control animals (Figure 2B)
Summary
Liver fibrosis is a hallmark of clonorchiasis suffered by millions people in Eastern Asian countries. Recent studies showed that the activation of TGF-β/Smad signaling pathway can potently regulate the hepatic fibrogenesis including Schistosoma spp. and Echinococcus multilocularis-caused liver fibrosis. Little is known to date about the expression of transforming growth factor-β (TGF-β) and other molecules in TGF-β/Smad signaling pathway which may play an important role in hepatic fibrosis caused by C. sinensis. Clonorchis sinensis is a food-borne zoonotic parasite, which is epidemic in some Eastern Asian countries including China, Korea, Japan, and Vietnam. Chronic infection with C. sinensis can potently lead to liver fibrosis which is marked with excessive accumulation of extracellular matrix components (ECM) due to an imbalance between its synthesis and degradation [2,7,8]. Molecular mechanism underlying fibrotic responses of hosts to these virulence factors is not fully elucidated
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
