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Early urinary candidate biomarker discovery in a rat thioacetamide-induced liver fibrosis model

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Abstract

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.

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Acknowledgements

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).

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  1. Department of Pathology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China

    Fanshuang Zhang

  2. Department of Pathophysiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, 10005, China

    Fanshuang Zhang, Yanying Ni, Yuan Yuan & Wei Yin

  3. Department of Pathology, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100050, China

    Yuan Yuan

  4. Department of Biochemistry and Molecular Biology, Beijing Normal University, Gene Engineering Drug and Biotechnology Beijing Key Laboratory, Beijing, 100875, China

    Youhe Gao

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  1. Fanshuang Zhang
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Zhang, F., Ni, Y., Yuan, Y. et al. Early urinary candidate biomarker discovery in a rat thioacetamide-induced liver fibrosis model. Sci. China Life Sci. 61, 1369–1381 (2018). https://doi.org/10.1007/s11427-017-9268-y

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