Early urinary candidate biomarker discovery in a rat thioacetamide-induced liver fibrosis model
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Biomarker is the change associated with the disease. Blood is relatively stable because of the homeostatic mechanisms of the body. However, urine accumulates changes of the body, which makes it a better early biomarker source. Liver fibrosis is a reversible pathological condition, whereas cirrhosis, the end-stage of liver fibrosis, is irreversible. Consequently, noninvasive early biomarkers for fibrosis are desperately needed. In this study, differential urinary proteins were identified in the thioacetamide liver fibrosis rat model using tandem mass tagging and two-dimensional liquid chromatography tandem mass spectrometry. A total of 766 urinary proteins were identified, 143 and 118 of which were significantly changed in the TAA 1-week and 3-week groups, respectively. Multiple reaction monitoring (MRM)-targeted proteomics was used to further validate the abundant differentially expressed proteins. A total of 40 urinary proteins were statistically significant, 15 of which had been previously reported as biomarkers of liver fibrosis, cirrhosis or other related diseases and 10 of which had been reported to be associated with the pathology and mechanism of liver fibrosis. These differential proteins were detected in urine before the alanine aminotransferase and aspartate transaminase changes in the serum and before fibrosis was observed upon hematoxylin and eosin (HE) and Masson’s staining.
Keywordsurine proteomics biomarker animal model liver fibrosis
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This work was supported by the National Key Research and Development Program of China (2016YFC1306300), the National Basic Research Program of China (2013CB530850), Beijing Natural Science Foundation (7173264, 7172076) and Funds from Beijing Normal University (11100704, 10300-310421102).
- Ariza, X., Graupera, I., Coll, M., Solà, E., Barreto, R., García, E., Moreira, R., Elia, C., Morales-Ruiz, M., Llopis, M., et al. (2016). Neutrophil gelatinase-associated lipocalin is a biomarker of acute-on-chronic liver failure and prognosis in cirrhosis. J Hepatol 65, 57–65.CrossRefPubMedGoogle Scholar
- Bracht, T., Schweinsberg, V., Trippler, M., Kohl, M., Ahrens, M., Padden, J., Naboulsi, W., Barkovits, K., Megger, D.A., Eisenacher, M., et al. (2015). Analysis of disease-associated protein expression using quantitative proteomics—fibulin-5 is expressed in association with hepatic fibrosis. J Proteome Res 14, 2278–2286.CrossRefPubMedGoogle Scholar
- Carter, W.G., Vigneswara, V., Newlaczyl, A., Wayne, D., Ahmed, B., Saddington, S., Brewer, C., Raut, N., Gerdes, H.K., Erdozain, A.M., et al. (2015). Isoaspartate, carbamoyl phosphate synthase-1, and carbonic anhydrase-III as biomarkers of liver injury. Biochem Biophys Res Commun 458, 626–631.CrossRefPubMedPubMedCentralGoogle Scholar
- Chai, Y.C., Jung, C.H., Lii, C.K., Ashraf, S.S., Hendrich, S., Wolf, B., Sies, H., and Thomas, J.A. (1991). Identification of an abundant S-thiolated rat liver protein as carbonic anhydrase III characterization of S-thiolation and dethiolation reactions. Arch Biochem Biophys 284, 270–278.CrossRefPubMedGoogle Scholar
- Gajbhiye, A., Dabhi, R., Taunk, K., Vannuruswamy, G., RoyChoudhury, S., Adhav, R., Seal, S., Mane, A., Bayatigeri, S., Santra, M.K., et al. (2016). Urinary proteome alterations in HER2 enriched breast cancer revealed by multipronged quantitative proteomics. Proteomics 16, 2403–2418.CrossRefPubMedGoogle Scholar
- Gao Y. (2014). Roadmap to the urine biomarker era. MOJ Proteom Bioinform 1, p.00005.Google Scholar
- Henkel, C., Schwamborn, K., Zimmermann, H.W., Tacke, F., Kühnen, E., Odenthal, M., Groseclose, M.R., Caprioli, R.M., and Weiskirchen, R. (2011). From proteomic multimarker profiling to interesting proteins: thymosin-β4 and kininogen-1 as new potential biomarkers for inflammatory hepatic lesions. J Cell Mol Med 15, 2176–2188.CrossRefPubMedPubMedCentralGoogle Scholar
- Huang, J.T.J., Chaudhuri, R., Albarbarawi, O., Barton, A., Grierson, C., Rauchhaus, P., Weir, C.J., Messow, M., Stevens, N., McSharry, C., et al. (2012). Clinical validity of plasma and urinary desmosine as biomarkers for chronic obstructive pulmonary disease. Thorax 67, 502–508.CrossRefPubMedPubMedCentralGoogle Scholar
- Li, X.N., Huang, C.T., Wang, X.H., Leng, X.S., Du, R.Y., Chen, Y.F., and Hou, X. (1990). Changes of blood humoral substances in experimental cirrhosis and their effects on portal hemodynamics. Chin Med J (Engl) 103, 970–977.Google Scholar
- Liu, E., Nisenblat, V., Farquhar, C., Fraser, I., Bossuyt, P.M., Johnson, N., and Hull, M.L. (2015). Urinary biomarkers for the non-invasive diagnosis of endometriosis. Cochrane Database Syst Rev (12), CD012019.Google Scholar
- MacLean, B., Tomazela, D.M., Shulman, N., Chambers, M., Finney, G.L., Frewen, B., Kern, R., Tabb, D.L., Liebler, D.C., and MacCoss, M.J. (2010). Skyline: an open source document editor for creating and analyzing targeted proteomics experiments. Bioinformatics 26, 966–968.CrossRefPubMedPubMedCentralGoogle Scholar
- Natarajan, S.K., Thomas, S., Ramamoorthy, P., Basivireddy, J., Pulimood, A.B., Ramachandran, A., and Balasubramanian, K.A. (2006). Oxidative stress in the development of liver cirrhosis: a comparison of two different experimental models. J Gastroenterol Hepatol 21, 947–957.CrossRefPubMedGoogle Scholar
- Noda, S., Masumi, S., Moriyama, M., Kannan, Y., Ohta, M., Sugano, T., and Yamate, J. (1996). Population of hepatic macrophages and response of perfused liver to platelet-activating factor during production of thioacetamide-induced cirrhosis in rats. Hepatology 24, 412–418.CrossRefPubMedGoogle Scholar
- Shao, C., Li, M., Li, X., Wei, L., Zhu, L., Yang, F., Jia, L., Mu, Y., Wang, J., Guo, Z., et al. (2011). A tool for biomarker discovery in the urinary proteome: a manually curated human and animal urine protein biomarker database. Mol Cell Proteomics 10, M111.010975.Google Scholar
- Tangkijvanich, P., Yee, H.F. (2002). Cirrhosis—can we reverse hepatic fibrosis. Eur J Surg Suppl (587), 100–112.Google Scholar
- Tennakoon, A.H., Izawa, T., Wijesundera, K.K., Murakami, H., Katou-Ichikawa, C., Tanaka, M., Golbar, H.M., Kuwamura, M., and Yamate, J. (2015). Immunohistochemical characterization of glial fibrillary acidic protein (GFAP)-expressing cells in a rat liver cirrhosis model induced by repeated injections of thioacetamide (TAA). Exp Toxicol Pathol 67, 53–63.CrossRefPubMedGoogle Scholar