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Transcriptional profiling of chronic clinical hepatic schistosomiasis japonica indicates reduced metabolism and immune responses

Published online by Cambridge University Press:  28 July 2015

GEOFFREY N. GOBERT ,
MELISSA L. BURKE ,
DONALD P. MCMANUS ,
MAGDA K. ELLIS ,
CANDY CHUAH ,
GRANT A. RAMM ,
YUANYUAN WANG  and
YUESHENG LI
GEOFFREY N. GOBERT*
Affiliation:
QIMR Berghofer Medical Research Institute, Brisbane, Qld 4006, Australia
MELISSA L. BURKE
Affiliation:
QIMR Berghofer Medical Research Institute, Brisbane, Qld 4006, Australia
DONALD P. MCMANUS*
Affiliation:
QIMR Berghofer Medical Research Institute, Brisbane, Qld 4006, Australia
MAGDA K. ELLIS
Affiliation:
QIMR Berghofer Medical Research Institute, Brisbane, Qld 4006, Australia
CANDY CHUAH
Affiliation:
QIMR Berghofer Medical Research Institute, Brisbane, Qld 4006, Australia School of Veterinary Sciences, The University of Queensland, Gatton, Qld 4343, Australia School of Medical Sciences, Universiti Sains Malaysia, 16150, Kelantan, Malaysia
GRANT A. RAMM
Affiliation:
QIMR Berghofer Medical Research Institute, Brisbane, Qld 4006, Australia
YUANYUAN WANG
Affiliation:
Hunan Institute of Parasitic Diseases, WHO Collaborating Centre for Research and Control of Schistosomiasis in the Lake Region, China
YUESHENG LI
Affiliation:
QIMR Berghofer Medical Research Institute, Brisbane, Qld 4006, Australia Hunan Institute of Parasitic Diseases, WHO Collaborating Centre for Research and Control of Schistosomiasis in the Lake Region, China
*
*Corresponding authors. QIMR Berghofer Medical Research Institute, Brisbane, Qld 4006, Australia. E-mail: Don.McManus@qimrberghofer.edu.au; Geoffrey.Gobert@qimrberghofer.edu.au
*Corresponding authors. QIMR Berghofer Medical Research Institute, Brisbane, Qld 4006, Australia. E-mail: Don.McManus@qimrberghofer.edu.au; Geoffrey.Gobert@qimrberghofer.edu.au
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Summary

Schistosomiasis is a significant cause of human morbidity and mortality. We performed a genome-wide transcriptional survey of liver biopsies obtained from Chinese patients with chronic schistosomiasis only, or chronic schistosomiasis with a current or past history of viral hepatitis B. Both disease groups were compared with patients with no prior history or indicators of any liver disease. Analysis showed in the main, downregulation in gene expression, particularly those involved in signal transduction via EIF2 signalling and mTOR signalling, as were genes associated with cellular remodelling. Focusing on immune associated pathways, genes were generally downregulated. However, a set of three genes associated with granulocytes, MMP7, CLDN7, CXCL6 were upregulated. Differential gene profiles unique to schistosomiasis included the gene Granulin which was decreased despite being generally considered a marker for liver disease, and IGBP2 which is associated with increased liver size, and was the most upregulated gene in schistosomiasis only patients, all of which presented with hepatomegaly. The unique features of gene expression, in conjunction with previous reports in the murine model of the cellular composition of granulomas, granuloma formation and recovery, provide an increased understanding of the molecular immunopathology and general physiological processes underlying hepatic schistosomiasis.

Keywords

SchistosomiasisSchistosomahepatic fibrosistranscriptomicsclinicalliver
Type
Research Article
Information
Parasitology , Volume 142 , Issue 12 , October 2015 , pp. 1453 - 1468
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Copyright
Copyright © Cambridge University Press 2015 

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References

REFERENCES

Affo, S., Dominguez, M., Lozano, J. J., Sancho-Bru, P., Rodrigo-Torres, D., Morales-Ibanez, O., Moreno, M., Millan, C., Loaeza-del-Castillo, A., Altamirano, J., Garcia-Pagan, J. C., Arroyo, V., Gines, P., Caballeria, J., Schwabe, R. F. and Bataller, R. (2013). Transcriptome analysis identifies TNF superfamily receptors as potential therapeutic targets in alcoholic hepatitis. Gut 62, 452–460.CrossRefGoogle ScholarPubMed
Balzar, M., Winter, M. J., de Boer, C. J. and Litvinov, S. V. (1999). The biology of the 17–1A antigen (Ep-CAM). Journal of Molecular Medicine (Berlin) 77, 699–712.Google Scholar
Banner, B. F., Savas, L., Zivny, J., Tortorelli, K. and Bonkovsky, H. L. (2000). Ubiquitin as a marker of cell injury in nonalcoholic steatohepatitis. American Journal of Clinical Pathology 114, 860–866.CrossRefGoogle ScholarPubMed
Bateman, A. and Bennett, H. P. (2009). The granulin gene family: from cancer to dementia. BioEssays 31, 1245–1254.CrossRefGoogle ScholarPubMed
Blackham, S., Baillie, A., Al-Hababi, F., Remlinger, K., You, S., Hamatake, R. and McGarvey, M. J. (2010). Gene expression profiling indicates the roles of host oxidative stress, apoptosis, lipid metabolism, and intracellular transport genes in the replication of hepatitis C virus. Journal of Virology 84, 5404–5414.CrossRefGoogle ScholarPubMed
Bose, S. K., Shrivastava, S., Meyer, K., Ray, R. B. and Ray, R. (2012). Hepatitis C virus activates the mTOR/S6K1 signaling pathway in inhibiting IRS-1 function for insulin resistance. Journal of Virology 86, 6315–6322.CrossRefGoogle ScholarPubMed
Bu, X., Jia, F., Wang, W., Guo, X., Wu, M. and Wei, L. (2007). Coupled down-regulation of mTOR and telomerase activity during fluorouracil-induced apoptosis of hepatocarcinoma cells. BMC Cancer 7, 208.CrossRefGoogle ScholarPubMed
Burke, M. L., Jones, M. K., Gobert, G. N., Li, Y. S., Ellis, M. K. and McManus, D. P. (2009). Immunopathogenesis of human schistosomiasis. Parasite Immunology 31, 163–176.Google Scholar
Burke, M. L., McManus, D. P., Ramm, G. A., Duke, M., Li, Y., Jones, M. K. and Gobert, G. N. (2010 a). Co-ordinated gene expression in the liver and spleen during Schistosoma japonicum infection regulates cell migration. PLoS Neglected Tropical Diseases 4, e686.Google Scholar
Burke, M. L., McManus, D. P., Ramm, G. A., Duke, M., Li, Y., Jones, M. K. and Gobert, G. N. (2010 b). Temporal expression of chemokines dictates the hepatic inflammatory infiltrate in a murine model of schistosomiasis. PLoS Neglected Tropical Diseases 4, e598.Google Scholar
Cao, Q. Y., Chen, F., Li, J., Wu, S. S., Wang, J. and Chen, Z. (2010). A microarray analysis of early activated pathways in concanavalin A-induced hepatitis. Journal of Zhejiang University. Science. B 11, 366–377.Google Scholar
Capell, A., Liebscher, S., Fellerer, K., Brouwers, N., Willem, M., Lammich, S., Gijselinck, I., Bittner, T., Carlson, A. M., Sasse, F., Kunze, B., Steinmetz, H., Jansen, R., Dormann, D., Sleegers, K., Cruts, M., Herms, J., Van Broeckhoven, C. and Haass, C. (2011). Rescue of progranulin deficiency associated with frontotemporal lobar degeneration by alkalizing reagents and inhibition of vacuolar ATPase. Journal of Neuroscience 31, 1885–1894.Google Scholar
Chen, F., Zhu, H. H., Zhou, L. F., Li, J., Zhao, L. Y., Wu, S. S., Wang, J., Liu, W. and Chen, Z. (2010). Genes related to the very early stage of ConA-induced fulminant hepatitis: a gene-chip-based study in a mouse model. BMC Genomics 11, 240.CrossRefGoogle Scholar
Chen, G., Chen, H., Wang, C., Peng, Y., Sun, L., Liu, H. and Liu, F. (2012). Rapamycin ameliorates kidney fibrosis by inhibiting the activation of mTOR signaling in interstitial macrophages and myofibroblasts. PLoS ONE 7, e33626.Google Scholar
Chen, L., Zhou, X. G., Zhou, X. Y., Zhu, C., Ji, C. B., Shi, C. M., Qiu, J. and Guo, X. R. (2013). Overexpression of C10orf116 promotes proliferation, inhibits apoptosis and enhances glucose transport in 3T3-L1 adipocytes. Molecular Medicine Reports 7, 1477–1481.Google Scholar
Cheung, S. T., Wong, S. Y., Leung, K. L., Chen, X., So, S., Ng, I. O. and Fan, S. T. (2004). Granulin-epithelin precursor overexpression promotes growth and invasion of hepatocellular carcinoma. Clinical Cancer Research 10, 7629–7636.Google Scholar
Chuah, C., Jones, M. K., Burke, M. L., Owen, H. C., Anthony, B. J., McManus, D. P., Ramm, G. A. and Gobert, G. N. (2013). Spatial and temporal transcriptomics of Schistosoma japonicum-induced hepatic granuloma formation reveals novel roles for neutrophils. Journal of Leukocyte Biology 94, 353–365.Google Scholar
Chuah, C., Jones, M. K., Burke, M. L., McManus, D. P. and Gobert, G. N. (2014 a). Cellular and chemokine-mediated regulation in schistosome-induced hepatic pathology. Trends in Parasitology 30, 141–150.Google Scholar
Chuah, C., Jones, M. K., Burke, M. L., McManus, D. P., Owen, H. C. and Gobert, G. N. (2014 b). Defining a pro-inflammatory neutrophil phenotype in response to schistosome eggs. Cellular Microbiology 16, 1666–1677.CrossRefGoogle ScholarPubMed
Dopper, E. G., Seelaar, H., Chiu, W. Z., de Koning, I., van Minkelen, R., Baker, M. C., Rozemuller, A. J., Rademakers, R. and van Swieten, J. C. (2011). Symmetrical corticobasal syndrome caused by a novel C.314dup progranulin mutation. Journal of Molecular Neuroscience 45, 354–358.Google Scholar
Fabre, V., Wu, H., PondTor, S., Coutinho, H., Acosta, L., Jiz, M., Olveda, R., Cheng, L., White, E. S., Jarilla, B., McGarvey, S. T., Friedman, J. F. and Kurtis, J. D. (2011). Tissue inhibitor of matrix-metalloprotease-1 predicts risk of hepatic fibrosis in human Schistosoma japonicum infection. Journal of Infectious Diseases 203, 707–714.Google Scholar
Firth, S. M. and Baxter, R. C. (2002). Cellular actions of the insulin-like growth factor binding proteins. Endocrine Reviews 23, 824–854.Google Scholar
Gryseels, B., Polman, K., Clerinx, J. and Kestens, L. (2006). Human schistosomiasis. Lancet 368, 1106–1118.Google Scholar
Heikens, M. J., Cao, T. M., Morita, C., Dehart, S. L. and Tsai, S. (2007). Penumbra encodes a novel tetraspanin that is highly expressed in erythroid progenitors and promotes effective erythropoiesis. Blood 109, 3244–3252.CrossRefGoogle ScholarPubMed
Huang, C. C., Chuang, J. H., Chou, M. H., Wu, C. L., Chen, C. M., Wang, C. C., Chen, Y. S., Chen, C. L. and Tai, M. H. (2005). Matrilysin (MMP-7) is a major matrix metalloproteinase upregulated in biliary atresia-associated liver fibrosis. Modern Pathology 18, 941–950.Google Scholar
Jiang, L., Xu, L., Mao, J., Li, J., Fang, L., Zhou, Y., Liu, W., He, W., Zhao, A. Z., Yang, J. and Dai, C. (2013). Rheb/mTORC1 signaling promotes kidney fibroblast activation and fibrosis. Journal of the American Society of Nephrology 24, 1114–1126.Google Scholar
Jimenez-Marin, A., Collado-Romero, M., Ramirez-Boo, M., Arce, C. and Garrido, J. J. (2009). Biological pathway analysis by arrayunlock and ingenuity pathway analysis. BMC Proceedings 3(Suppl. 4), S6.Google Scholar
Katz, N., Chaves, A. and Pellegrino, J. (1972). A simple device for quantitative stool thick-smear technique in Schistosomiasis mansoni. Revista do Instituto de Medicina Tropical de Sao Paulo 14, 397–400.Google ScholarPubMed
Khosla, S., Hassoun, A. A., Baker, B. K., Liu, F., Zein, N. N., Whyte, M. P., Reasner, C. A., Nippoldt, T. B., Tiegs, R. D., Hintz, R. L. and Conover, C. A. (1998). Insulin-like growth factor system abnormalities in hepatitis C-associated osteosclerosis. Potential insights into increasing bone mass in adults. Journal of Clinical Investigation 101, 2165–2173.Google Scholar
Kimura, O., Kondo, Y., Kogure, T., Kakazu, E., Ninomiya, M., Iwata, T., Morosawa, T. and Shimosegawa, T. (2014). Expression of EpCAM increases in the Hepatitis B related and the treatment-resistant hepatocellular carcinoma. BioMed Research International 2014, 172913.Google Scholar
Krastev, Z. (1998). Liver damage score--a new index for evaluation of the severity of chronic liver diseases. Hepato-Gastroenterology 45, 160–169.Google Scholar
Laplante, M. and Sabatini, D. M. (2012). mTOR signaling in growth control and disease. Cell 149, 274–293.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.Google Scholar
Lichtinghagen, R., Michels, D., Haberkorn, C. I., Arndt, B., Bahr, M., Flemming, P., Manns, M. P. and Boeker, K. H. (2001). Matrix metalloproteinase (MMP)-2, MMP-7, and tissue inhibitor of metalloproteinase-1 are closely related to the fibroproliferative process in the liver during chronic hepatitis C. Journal of Hepatology 34, 239–247.Google Scholar
McDonald, E. A., Cheng, L., Jarilla, B., Sagliba, M. J., Gonzal, A., Amoylen, A. J., Olveda, R., Acosta, L., Baylink, D., White, E. S., Friedman, J. F. and Kurtis, J. D. (2014). Maternal infection with Schistosoma japonicum induces a profibrotic response in neonates. Infection and Immunity 82, 350–355.Google Scholar
Murray, C. J., Vos, T., Lozano, R., Naghavi, M., Flaxman, A. D., Michaud, C., Ezzati, M., Shibuya, K., Salomon, J. A., Abdalla, S., Aboyans, V., Abraham, J., Ackerman, I., Aggarwal, R., Ahn, S. Y., Ali, M. K., Alvarado, M., Anderson, H. R., Anderson, L. M., Andrews, K. G., Atkinson, C., Baddour, L. M., Bahalim, A. N., Barker-Collo, S., Barrero, L. H., Bartels, D. H., Basanez, M. G., Baxter, A., Bell, M. L., Benjamin, E. J., et al. (2013). Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990–2010: a systematic analysis. Lancet 380, 2197–2223.Google Scholar
Nissim, O., Melis, M., Diaz, G., Kleiner, D. E., Tice, A., Fantola, G., Zamboni, F., Mishra, L. and Farci, P. (2012). Liver regeneration signature in hepatitis B virus (HBV)-associated acute liver failure identified by gene expression profiling. PLoS ONE 7, e49611.Google Scholar
Perry, C. R., Burke, M. L., Stenzel, D. J., McManus, D. P., Ramm, G. A. and Gobert, G. N. (2011). Differential expression of chemokine and matrix re-modelling genes is associated with contrasting schistosome-induced hepatopathology in murine models. PLoS Neglected Tropical Diseases 5, e1178.Google Scholar
Raychoudhuri, A., Shrivastava, S., Steele, R., Kim, H., Ray, R. and Ray, R. B. (2011). ISG56 and IFITM1 proteins inhibit hepatitis C virus replication. Journal of Virology 85, 12881–12889.Google Scholar
Revillard, J. P. (1980). Significance of beta 2-microglobulin in liver diseases. Vox Sanguinis 38, 339–342.Google Scholar
Rosas, I. O., Richards, T. J., Konishi, K., Zhang, Y., Gibson, K., Lokshin, A. E., Lindell, K. O., Cisneros, J., Macdonald, S. D., Pardo, A., Sciurba, F., Dauber, J., Selman, M., Gochuico, B. R. and Kaminski, N. (2008). MMP1 and MMP7 as potential peripheral blood biomarkers in idiopathic pulmonary fibrosis. PLoS Medicine 5, e93.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.Google Scholar
Sahin, H., Trautwein, C. and Wasmuth, H. E. (2010). Functional role of chemokines in liver disease models. Nature Reviews. Gastroenterology and Hepatology 7, 682–690.Google Scholar
Sharp, Z. D. and Bartke, A. (2005). Evidence for down-regulation of phosphoinositide 3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR)-dependent translation regulatory signaling pathways in Ames dwarf mice. Journals of Gerontology. Series A, Biological Sciences and Medical Sciences 60, 293–300.CrossRefGoogle ScholarPubMed
Smout, M. J., Laha, T., Mulvenna, J., Sripa, B., Suttiprapa, S., Jones, A., Brindley, P. J. and Loukas, A. (2009). A granulin-like growth factor secreted by the carcinogenic liver fluke, Opisthorchis viverrini, promotes proliferation of host cells. PLoS Pathogens 5, e1000611.Google Scholar
Song, J. W., Do, K. H., Jang, S. J., Colby, T. V., Han, S. and Kim, D. S. (2013). Blood biomarkers MMP-7 and SP-A: predictors of outcome in idiopathic pulmonary fibrosis. Chest 143, 1422–1429.Google Scholar
Tacke, F., Zimmermann, H. W., Trautwein, C. and Schnabl, B. (2011). CXCL5 plasma levels decrease in patients with chronic liver disease. Journal of Gastroenterology and Hepatology 26, 523–529.Google Scholar
Wang, Z., Jin, W., Jin, H. and Wang, X. (2014). mTOR in viral hepatitis and hepatocellular carcinoma: function and treatment. Biomed Res Int 2014, 735672.Google Scholar
Wendel, A. A., Lewin, T. M. and Coleman, R. A. (2009). Glycerol-3-phosphate acyltransferases: rate limiting enzymes of triacylglycerol biosynthesis. Biochimica et Biophysica Acta 1791, 501–506.Google Scholar
Whaley-Connell, A., Habibi, J., Panfili, Z., Hayden, M. R., Bagree, S., Nistala, R., Hyder, S., Krueger, B., Demarco, V., Pulakat, L., Ferrario, C. M., Parrish, A. and Sowers, J. R. (2011). Angiotensin II activation of mTOR results in tubulointerstitial fibrosis through loss of N-cadherin. American Journal of Nephrology 34, 115–125.Google Scholar
Wilson, M. S., Mentink-Kane, M. M., Pesce, J. T., Ramalingam, T. R., Thompson, R. and Wynn, T. A. (2007). Immunopathology of schistosomiasis. Immunology and Cell Biology 85, 148–154.Google Scholar
Wu, C., Macleod, I. and Su, A. I. (2013). BioGPS and MyGene.info: organizing online, gene-centric information. Nucleic Acids Research 41(Database issue), D561–D565.Google Scholar
Yamashita, T., Budhu, A., Forgues, M. and Wang, X. W. (2007). Activation of hepatic stem cell marker EpCAM by Wnt-beta-catenin signaling in hepatocellular carcinoma. Cancer Research 67, 10831–10839.Google Scholar
Yen, C. J., Lin, Y. J., Yen, C. S., Tsai, H. W., Tsai, T. F., Chang, K. Y., Huang, W. C., Lin, P. W., Chiang, C. W. and Chang, T. T. (2012). Hepatitis B virus X protein upregulates mTOR signaling through IKKbeta to increase cell proliferation and VEGF production in hepatocellular carcinoma. PLoS ONE 7, e41931.Google Scholar
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