Hostname: page-component-78c5997874-xbtfd Total loading time: 0 Render date: 2024-11-15T23:24:39.417Z Has data issue: false hasContentIssue false
  • English
  • Français

Expression of heat shock protein 47, transforming growth factor-beta 1, and connective tissue growth factor in liver tissue of patients with Schistosoma japonicum-induced hepatic fibrosis

Published online by Cambridge University Press:  11 August 2014

LAN LI ,
TING WU ,
JIAQUAN HUANG ,
KE MA ,
LEI XU ,
HONGWU WANG ,
XIANGXUE FAN ,
RAN TAO ,
GUO AI  and
QIN NING
LAN LI
Affiliation:
Department of Infectious Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China
TING WU
Affiliation:
Department of Infectious Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China
JIAQUAN HUANG
Affiliation:
Department of Infectious Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China
KE MA
Affiliation:
Department of Infectious Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China
LEI XU
Affiliation:
Department of Emergency, Xiangyang No.1 People's Hospital, Xiangyang, Hubei, 442000, China
HONGWU WANG
Affiliation:
Department of Infectious Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China
XIANGXUE FAN
Affiliation:
Department of Infectious Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China
RAN TAO
Affiliation:
Department of Infectious Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China
GUO AI
Affiliation:
Department of Infectious Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China
QIN NING*
Affiliation:
Department of Infectious Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China
*
*Corresponding author. Department of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, 430030, Wuhan, P.R. China. E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Summary

To detect the expression of pro-fibrotic molecules, such as heat shock protein 47 (Hsp47), transforming growth factor-beta 1 (TGF-β1) and connective tissue growth factor (CTGF) in liver specimens, and analyse their correlations with the progression of schistosomal hepatic fibrosis, liver biopsy was performed in 42 chronic schistosomiasis (CS) patients, 16 chronic hepatitis B (CHB) patients and five healthy individuals (HI). Immunohistochemistry (IHC) analyses displayed that the expression of Hsp47, TGF-β1 and CTGF was increased in CS and CHB patients compared with HI. Using real-time PCR, the mRNA levels of Hsp47, TGF-β1 and CTGF were higher in CS patients compared with HI. In CS patients, the mRNA levels of these genes were correlated with the stage of fibrosis, and TGF-β1 mRNA expression was associated with the grade of inflammation. Additional analyses indicated that the mRNA levels of Hsp47 and CTGF were highly correlated with liver stiffness value and spleen thickness diameter, both of which represented the severity of fibrosis. In conclusion, the three molecules are involved in the pathogenesis of hepatic fibrosis infected by Schistosoma japonicum. TGF-β1 participates not only in the inflammatory process, but also in the fibrotic process in which Hsp47 and CTGF probably play a key role.

Keywords

Hepatic fibrosisSchistosoma japonicumheat shock protein 47transforming growth factor-beta 1connective tissue growth factor
Type
Research Article
Information
Parasitology , Volume 142 , Issue 2 , February 2015 , pp. 341 - 351
Check for updates
Copyright
Copyright © Cambridge University Press 2014 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Abou-Shady, M., Friess, H., Zimmermann, A., di Mola, F. F., Guo, X. Z., Baer, H. U. and Buchler, M. W. (2000). Connective tissue growth factor in human liver cirrhosis. Liver 20, 296–304.CrossRefGoogle ScholarPubMed
Andrade, Z. A. (2009). Schistosomiasis and liver fibrosis. Parasite Immunology 31, 656–663. doi: 10.1111/j.1365-3024.2009.01157.x.CrossRefGoogle ScholarPubMed
Banner, B. F., Allan, C., Savas, L., Baker, S., Barnard, G. and Bonkovsky, H. L. (1997). Inflammatory markers in chronic hepatitis C. Virchows Archiv 431, 181–187.CrossRefGoogle ScholarPubMed
Brown, K. E., Broadhurst, K. A., Mathahs, M. M., Brunt, E. M. and Schmidt, W. N. (2005). Expression of Hsp47, a collagen-specific chaperone, in normal and diseased human liver. Laboratory Investigation 85, 789–797. doi: 10.1038/labinvest.3700271.Google Scholar
Castera, L. and Pinzani, M. (2010). Biopsy and non-invasive methods for the diagnosis of liver fibrosis: does it take two to tango? Gut 59, 861–866. doi: 10.1136/gut.2010.214650.Google Scholar
Castilla, A., Prieto, J. and Fausto, N. (1991). Transforming growth factors beta 1 and alpha in chronic liver disease. Effects of interferon alpha therapy. New England Journal of Medicine 324, 933–940. doi: 10.1056/NEJM199104043241401.Google Scholar
Cheever, A. W. (1985). Schistosoma japonicum: the pathology of experimental infection. Experimental Parasitology 59, 1–11.Google Scholar
Colak, Y., Senates, E., Coskunpinar, E., Oltulu, Y. M., Zemheri, E., Ozturk, O., Doganay, L., Mesci, B., Yilmaz, Y., Enc, F. Y., Kiziltas, S., Ulasoglu, C. and Tuncer, I. (2012). Concentrations of connective tissue growth factor in patients with nonalcoholic fatty liver disease: association with liver fibrosis. Disease Markers 33, 77–83. doi: 10.3233/DMA-2012-0907.Google Scholar
De Cock, K. M. (1986). Hepatosplenic schistosomiasis: a clinical review. Gut 27, 734–745.CrossRefGoogle ScholarPubMed
Deng, Y. H., Pu, C. L., Li, Y. C., Zhu, J., Xiang, C., Zhang, M. M. and Guo, C. B. (2011). Analysis of biliary epithelial-mesenchymal transition in portal tract fibrogenesis in biliary atresia. Digestive Diseases and Sciences 56, 731–740. doi: 10.1007/s10620-010-1347-6.CrossRefGoogle ScholarPubMed
Desmet, V. J., Gerber, M., Hoofnagle, J. H., Manns, M. and Scheuer, P. J. (1994). Classification of chronic hepatitis: diagnosis, grading and staging. Hepatology 19, 1513–1520.CrossRefGoogle ScholarPubMed
Ding, H., Wu, T., Ma, K., Wang, X., Wu, Z., Guo, W., Qi, J. and Ning, Q. (2012). Noninvasive measurement of liver fibrosis by transient elastography and influencing factors in patients with chronic hepatitis B-A single center retrospective study of 466 patients. Journal of Huazhong University of Science and Technology Medical Sciences 32, 69–74. doi: 10.1007/s11596-012-0012-z.Google Scholar
Ding, Z. Y., Jin, G. N., Liang, H. F., Wang, W., Chen, W. X., Datta, P. K., Zhang, M. Z., Zhang, B. and Chen, X. P. (2013). Transforming growth factor beta induces expression of connective tissue growth factor in hepatic progenitor cells through Smad independent signaling. Cellular Signalling 25, 1981–1992. doi: 10.1016/j.cellsig.2013.05.027.Google Scholar
El-Bassiouni, N. E., Nosseir, M. M., Madkour, M. E., Zoheiry, M. M., Bekheit, I. W., Ibrahim, R. A., Ibrahim, I. M. and El Bassiouny, A. E. (2012). Role of fibrogenic markers in chronic hepatitis C and associated hepatocellular carcinoma. Molecular Biology Reports 39, 6843–6850. doi: 10.1007/s11033-012-1509-z.CrossRefGoogle ScholarPubMed
Farrington, C., Novak, D., Liu, C. and Haafiz, A. B. (2010). Immunohistochemical localization of transforming growth factor beta-1 and its relationship with collagen expression in advanced liver fibrosis due to biliary atresia. Clinical and Experimental Gastroenterology 3, 185–191. doi: 10.2147/CEG.S14220.Google Scholar
Flisiak, R. and Prokopowicz, D. (2000). Transforming growth factor-beta1 as a surrogate marker of hepatic dysfunction in chronic liver diseases. Clinical Chemistry and Laboratory Medicine 38, 1129–1131. doi: 10.1515/CCLM.2000.170.Google Scholar
Friedman, S. L. (2008). Mechanisms of hepatic fibrogenesis. Gastroenterology 134, 1655–1669. doi: 10.1053/j.gastro.2008.03.003.Google Scholar
Gressner, O. A., Lahme, B., Demirci, I., Gressner, A. M. and Weiskirchen, R. (2007). Differential effects of TGF-beta on connective tissue growth factor (CTGF/CCN2) expression in hepatic stellate cells and hepatocytes. Journal of Hepatology 47, 699–710. doi: 10.1016/j.jhep.2007.05.015.Google Scholar
Guo-Qiu, W., Nai-Feng, L., Xiao-Bo, V., Linxian, L., Chen, Z., Lixia, G. and Zhao, L. (2010). The level of connective tissue growth factor in sera of patients with hepatitis B virus strongly correlates with stage of hepatic fibrosis. Viral Immunology 23, 71–78. doi: 10.1089/vim.2009.0067.Google Scholar
Hao, C., Xie, Y., Peng, M., Ma, L., Zhou, Y., Zhang, Y., Kang, W., Wang, J., Bai, X., Wang, P. and Jia, Z. (2013). Inhibition of connective tissue growth factor suppresses hepatic stellate cell activation in vitro and prevents liver fibrosis in vivo . Clinical and Experimental Medicine 14, 141–150. doi: 10.1007/s10238-013-0229-6.CrossRefGoogle ScholarPubMed
Heid, C. A., Stevens, J., Livak, K. J. and Williams, P. M. (1996). Real time quantitative PCR. Genome Research 6, 986–994.CrossRefGoogle ScholarPubMed
Honzawa, Y., Nakase, H., Matsumura, K., Yamamoto, S., Uza, N., Matsuura, M. and Chiba, T. (2011). IL-17 promotes HSP47 expression and intestinal fibrosis in Crohn's disease. Gastroenterology 140, S-493. doi: 10.1016/S0016-5085(11)62035-0.Google Scholar
Huang, J. Q., Zhu, J., Li, L., Jiao, Y. T., Xu, L., Tao, R., Fan, X. X., Ma, K., Guo, W. and Ning, Q. (2012). Expression of transforming growth factor-beta1 and connective tissue growing factor in schistosomal hepatic fibrosis of mice. Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi 30, 20–26.Google Scholar
Huang, J. Q., Tao, R., Li, L., Ma, K., Xu, L., Ai, G., Fan, X. X., Jiao, Y. T. and Ning, Q. (2014). Involvement of heat shock protein 47 in Schistosoma japonicum-induced hepatic fibrosis in mice. International Journal for Parasitology 44, 23–35. doi: 10.1016/j.ijpara.2013.08.009.Google Scholar
Ishii, H., Mukae, H., Kakugawa, T., Iwashita, T., Kaida, H., Fujii, T., Hayashi, T., Kadota, J. and Kohno, S. (2003). Increased expression of collagen-binding heat shock protein 47 in murine bleomycin-induced pneumopathy. American Journal of Physiology. Lung Cellular and Molecular Physiology 285, L957–L963. doi: 10.1152/ajplung.00305.2002.Google Scholar
Kanzler, S., Baumann, M., Schirmacher, P., Dries, V., Bayer, E., Gerken, G., Dienes, H. P. and Lohse, A. W. (2001). Prediction of progressive liver fibrosis in hepatitis C infection by serum and tissue levels of transforming growth factor-beta. Journal of Viral Hepatitis 8, 430–437.CrossRefGoogle ScholarPubMed
Kawada, N., Kuroki, T., Kobayashi, K., Inoue, M., Nakatani, K., Kaneda, K. and Nagata, K. (1996). Expression of heat-shock protein 47 in mouse liver. Cell and Tissue Research 284, 341–346.Google Scholar
Kisseleva, T. and Brenner, D. A. (2007). Role of hepatic stellate cells in fibrogenesis and the reversal of fibrosis. Journal of Gastroenterology and Hepatology 22 (Suppl. 1), S73–S78. doi: 10.1111/j.1440-1746.2006.04658.x.Google Scholar
Krizhanovsky, V., Yon, M., Dickins, R. A., Hearn, S., Simon, J., Miething, C., Yee, H., Zender, L. and Lowe, S. W. (2008). Senescence of activated stellate cells limits liver fibrosis. Cell 134, 657–667. doi: 10.1016/j.cell.2008.06.049.Google Scholar
Li, Y., Chen, D., Ross, A. G., Burke, M. L., Yu, X., Li, R. S., Zhou, J. and McManus, D. P. (2011). Severe hepatosplenic schistosomiasis: clinicopathologic study of 102 cases undergoing splenectomy. Human Pathology 42, 111–119. doi: 10.1016/j.humpath.2010.05.020.Google Scholar
Lu, L. G., Zeng, M. D., Wan, M. B., Li, C. Z., Mao, Y. M., Li, J. Q., Qiu, D. K., Cao, A. P., Ye, J., Cai, X., Chen, C. W., Wang, J. Y., Wu, S. M., Zhu, J. S. and Zhou, X. Q. (2003). Grading and staging of hepatic fibrosis, and its relationship with noninvasive diagnostic parameters. World Journal of Gastroenterology 9, 2574–2578.CrossRefGoogle ScholarPubMed
Malizia, G., Brunt, E. M., Peters, M. G., Rizzo, A., Broekelmann, T. J. and McDonald, J. A. (1995). Growth factor and procollagen type I gene expression in human liver disease. Gastroenterology 108, 145–156.CrossRefGoogle ScholarPubMed
Masuda, H., Fukumoto, M., Hirayoshi, K. and Nagata, K. (1994). Coexpression of the collagen-binding stress protein HSP47 gene and the alpha 1(I) and alpha 1(III) collagen genes in carbon tetrachloride-induced rat liver fibrosis. Journal of Clinical Investigation 94, 2481–2488. doi: 10.1172/JCI117617.Google Scholar
McManus, D. P., Gray, D. J., Li, Y., Feng, Z., Williams, G. M., Stewart, D., Rey-Ladino, J. and Ross, A. G. (2010). Schistosomiasis in the People's Republic of China: the era of the Three Gorges Dam. Clinical Microbiology Reviews 23, 442–466. doi: 10.1128/CMR.00044-09.Google Scholar
Morais, C. N., Carvalho Bde, M., Melo, W. G., Melo, F. L., Lopes, E. P., Domingues, A. L., Juca, N., Martins, J. R., Diniz, G. T. and Montenegro, S. M. (2010). Correlation of biological serum markers with the degree of hepatic fibrosis and necroinflammatory activity in hepatitis C and schistosomiasis patients. Memórias do Instituto Oswaldo Cruz 105, 460–466.Google Scholar
Moriyama, T., Kawada, N., Ando, A., Yamauchi, A., Horio, M., Nagata, K., Imai, E. and Hori, M. (1998). Up-regulation of HSP47 in the mouse kidneys with unilateral ureteral obstruction. Kidney International 54, 110–119. doi: 10.1046/j.1523-1755.1998.00XXX.x.CrossRefGoogle ScholarPubMed
Nishikawa, Y., Takahara, Y., Asada, S., Shigenaga, A., Otaka, A., Kitagawa, K. and Koide, T. (2010). A structure-activity relationship study elucidating the mechanism of sequence-specific collagen recognition by the chaperone HSP47. Bioorganic and Medicinal Chemistry 18, 3767–3775. doi: 10.1016/j.bmc.2010.04.054.Google Scholar
Piao, R. L., Brigstock, D. R., Zhu, J., Zhang, M. L. and Gao, R. P. (2012). Clinical significance of connective tissue growth factor in hepatitis B virus-induced hepatic fibrosis. World Journal of Gastroenterology 18, 2280–2286. doi: 10.3748/wjg.v18.i18.2280.Google Scholar
Piekarska, A., Piekarski, J., Omulecka, A., Szymczak, W. and Kubiak, R. (2006). Expression of Ki-67, transforming growth factor beta1, and B-cell lymphoma-leukemia-2 in liver tissue of patients with chronic liver diseases. Journal of Gastroenterology and Hepatology 21, 700–710. doi: 10.1111/j.1440-1746.2006.04149.x.Google Scholar
Razzaque, M. S. and Ahmed, A. R. (2002). Collagens, collagen-binding heat shock protein 47 and transforming growth factor-beta 1 are induced in cicatricial pemphigoid: possible role(s) in dermal fibrosis. Cytokine 17, 311–316. doi: 10.1006/cyto.2002.1020.Google Scholar
Ross, A. G., Bartley, P. B., Sleigh, A. C., Olds, G. R., Li, Y., Williams, G. M. and McManus, D. P. (2002). Schistosomiasis. New England Journal of Medicine 346, 1212–1220. doi: 10.1056/NEJMra012396.Google Scholar
Roth, S., Michel, K. and Gressner, A. M. (1998). (Latent) transforming growth factor beta in liver parenchymal cells, its injury-dependent release, and paracrine effects on rat hepatic stellate cells. Hepatology 27, 1003–1012. doi: 10.1002/hep.510270416.Google Scholar
Sanchez-Lopez, E., Rayego, S., Rodrigues-Diez, R., Rodriguez, J. S., Rodriguez-Vita, J., Carvajal, G., Aroeira, L. S., Selgas, R., Mezzano, S. A., Ortiz, A., Egido, J. and Ruiz-Ortega, M. (2009). CTGF promotes inflammatory cell infiltration of the renal interstitium by activating NF-kappaB. Journal of the American Society of Nephrology 20, 1513–1526. doi: 10.1681/ASN.2008090999.Google Scholar
Sasaki, H., Sato, T., Yamauchi, N., Okamoto, T., Kobayashi, D., Iyama, S., Kato, J., Matsunaga, T., Takimoto, R., Takayama, T., Kogawa, K., Watanabe, N. and Niitsu, Y. (2002). Induction of heat shock protein 47 synthesis by TGF-beta and IL-1 beta via enhancement of the heat shock element binding activity of heat shock transcription factor 1. Journal of Immunology 168, 5178–5183.CrossRefGoogle ScholarPubMed
Sato, Y., Murase, K., Kato, J., Kobune, M., Sato, T., Kawano, Y., Takimoto, R., Takada, K., Miyanishi, K., Matsunaga, T., Takayama, T. and Niitsu, Y. (2008). Resolution of liver cirrhosis using vitamin A-coupled liposomes to deliver siRNA against a collagen-specific chaperone. Nature Biotechnology 26, 431–442. doi: 10.1038/Nbt1396.Google Scholar
Steinmann, P., Keiser, J., Bos, R., Tanner, M. and Utzinger, J. (2006). Schistosomiasis and water resources development: systematic review, meta-analysis, and estimates of people at risk. Lancet Infectious Diseases 6, 411–425. doi: 10.1016/S1473-3099(06)70521-7.Google Scholar
Tasab, M., Batten, M. R. and Bulleid, N. J. (2000). Hsp47: a molecular chaperone that interacts with and stabilizes correctly-folded procollagen. EMBO Journal 19, 2204–2211. doi: 10.1093/emboj/19.10.2204.CrossRefGoogle ScholarPubMed
Turato, C., Calabrese, F., Biasiolo, A., Quarta, S., Ruvoletto, M., Tono, N., Paccagnella, D., Fassina, G., Merkel, C., Harrison, T. J., Gatta, A. and Pontisso, P. (2010). SERPINB3 modulates TGF-beta expression in chronic liver disease. Laboratory Investigation 90, 1016–1023. doi: 10.1038/labinvest.2010.55.Google Scholar
van de Bovenkamp, M., Groothuis, G. M., Meijer, D. K. and Olinga, P. (2008). Liver slices as a model to study fibrogenesis and test the effects of anti-fibrotic drugs on fibrogenic cells in human liver. Toxicology In Vitro 22, 771–778. doi: 10.1016/j.tiv.2007.11.019.Google Scholar
Yuan, G., Duan, Y., Wang, F., Liang, S. Sr. and Zhu, L. (2002). Prevention and treatment of HBV reinfection following liver transplantation. Zhonghua Gan Zang Bing Za Zhi 10, 14–16.Google Scholar
Supplementary material: File

Li Supplementary Material

Figure Captions

Download Li Supplementary Material(File)
File 28.2 KB
Supplementary material: Image

Li Supplementary Material

Figure S1

Download Li Supplementary Material(Image)
Image 218.2 KB
Supplementary material: Image

Li Supplementary Material

Figure S2

Download Li Supplementary Material(Image)
Image 407 KB