The expression dynamics of transforming growth factor-β/Smad signaling in the liver fibrosis experimentally caused by Clonorchis sinensis
Abstract Background 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 multiloculari...
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| Format: | Article |
| Language: | English |
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BMC
2015-02-01
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| Series: | Parasites & Vectors |
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| Online Access: | https://doi.org/10.1186/s13071-015-0675-y |
| _version_ | 1827933732680499200 |
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| author | Chao Yan Lin Wang Bo Li Bei-Bei Zhang Bo Zhang Yan-Hong Wang Xiang-Yang Li Jia-Xu Chen Ren-Xian Tang Kui-Yang Zheng |
| author_facet | Chao Yan Lin Wang Bo Li Bei-Bei Zhang Bo Zhang Yan-Hong Wang Xiang-Yang Li Jia-Xu Chen Ren-Xian Tang Kui-Yang Zheng |
| author_sort | Chao Yan |
| collection | DOAJ |
| description | Abstract Background 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. 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. Methods A 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. Results The 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. Conclusions The 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. |
| first_indexed | 2024-03-13T07:28:54Z |
| format | Article |
| id | doaj.art-e3b5c6a373524b20a9628e3ff05208f9 |
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| issn | 1756-3305 |
| language | English |
| last_indexed | 2024-03-13T07:28:54Z |
| publishDate | 2015-02-01 |
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| spelling | doaj.art-e3b5c6a373524b20a9628e3ff05208f92023-06-04T11:14:47ZengBMCParasites & Vectors1756-33052015-02-01811810.1186/s13071-015-0675-yThe expression dynamics of transforming growth factor-β/Smad signaling in the liver fibrosis experimentally caused by Clonorchis sinensisChao Yan0Lin Wang1Bo Li2Bei-Bei Zhang3Bo Zhang4Yan-Hong Wang5Xiang-Yang Li6Jia-Xu Chen7Ren-Xian Tang8Kui-Yang Zheng9Department of Pathogenic Biology and Immunology, Laboratory of Infection and Immunity, Xuzhou Medical CollegeDepartment of Pathogenic Biology and Immunology, Laboratory of Infection and Immunity, Xuzhou Medical CollegeDepartment of Pathogenic Biology and Immunology, Laboratory of Infection and Immunity, Xuzhou Medical CollegeDepartment of Pathogenic Biology and Immunology, Laboratory of Infection and Immunity, Xuzhou Medical CollegeDepartment of Pathogenic Biology and Immunology, Laboratory of Infection and Immunity, Xuzhou Medical CollegeDepartment of Pathogenic Biology and Immunology, Laboratory of Infection and Immunity, Xuzhou Medical CollegeDepartment of Pathogenic Biology and Immunology, Laboratory of Infection and Immunity, Xuzhou Medical CollegeLaboratory of Parasite and Vector Biology, National Institute of Parasitic Diseases, Chinese Center for Disease Control and PreventionDepartment of Pathogenic Biology and Immunology, Laboratory of Infection and Immunity, Xuzhou Medical CollegeDepartment of Pathogenic Biology and Immunology, Laboratory of Infection and Immunity, Xuzhou Medical CollegeAbstract Background 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. 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. Methods A 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. Results The 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. Conclusions The 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.https://doi.org/10.1186/s13071-015-0675-yClonorchis sinensisLiver fibrosisTransforming growth factor-βSmads |
| spellingShingle | Chao Yan Lin Wang Bo Li Bei-Bei Zhang Bo Zhang Yan-Hong Wang Xiang-Yang Li Jia-Xu Chen Ren-Xian Tang Kui-Yang Zheng The expression dynamics of transforming growth factor-β/Smad signaling in the liver fibrosis experimentally caused by Clonorchis sinensis Parasites & Vectors Clonorchis sinensis Liver fibrosis Transforming growth factor-β Smads |
| title | The expression dynamics of transforming growth factor-β/Smad signaling in the liver fibrosis experimentally caused by Clonorchis sinensis |
| title_full | The expression dynamics of transforming growth factor-β/Smad signaling in the liver fibrosis experimentally caused by Clonorchis sinensis |
| title_fullStr | The expression dynamics of transforming growth factor-β/Smad signaling in the liver fibrosis experimentally caused by Clonorchis sinensis |
| title_full_unstemmed | The expression dynamics of transforming growth factor-β/Smad signaling in the liver fibrosis experimentally caused by Clonorchis sinensis |
| title_short | The expression dynamics of transforming growth factor-β/Smad signaling in the liver fibrosis experimentally caused by Clonorchis sinensis |
| title_sort | expression dynamics of transforming growth factor β smad signaling in the liver fibrosis experimentally caused by clonorchis sinensis |
| topic | Clonorchis sinensis Liver fibrosis Transforming growth factor-β Smads |
| url | https://doi.org/10.1186/s13071-015-0675-y |
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