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Proteomic Identification Network Analysis of Haptoglobin as a Key Regulator Associated with Liver Fibrosis

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Abstract

Liver fibrosis (LF) is the final stage of liver dysfunction, characterized by diffuse fibrosis which is the main response to the liver injury. Haptoglobin (HP) protein, produced as an acute phase reactant during LF, preventing liver damage, may be potential molecular targets for early LF diagnostics and therapeutic applications. However, protein networks associated with the HP are largely unknown. To address this issue, we used a pathological mouse model of LF that was induced by treatment with carbon tetrachloride for 8 days. HP protein was separated and identified by two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization time-of-flight/time-of-flight mass spectrometry. HP protein was subjected to functional pathway analysis using STRING and Cytoscape software for better understanding of the protein–protein interaction (PPI) networks in biological context. Bioinformatics analyses revealed that HP expression associated with fibrosis was upregulated, and suggested that HP responsible for fibrosis may precede the onset and progression of LF. Using the web-based database, functional pathway analysis suggested the modulation of multiple vital physiological pathways, including antioxidation immunity, signal transduction, metabolic process, energy production, cell apoptosis, oxidation reduction, DNA repair process, cell communication, and regulation of cellular process. The generation of protein interaction networks clearly enhances the interpretation and understanding of the molecular mechanisms of HP. HP protein represents targets for further experimental investigation that will provide biological insight and potentially could be exploited for novel therapeutic approaches to combat LF.

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Acknowledgments

This work was supported by grants from the Key Program of Natural Science Foundation of State (grant no. 90709019), the National Specific Program on the Subject of Public Welfare (grant no. 200807014), National Key Subject of Drug Innovation (grant no. 2009ZX09502-005), and National Program on Key Basic Research Project of China (grant no. 2005CB523406).

Conflict of interest

The authors declare that they have no competing interests.

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Authors and Affiliations

  1. National TCM Key Lab of Serum Pharmacochemistry, Heilongjiang University of Chinese Medicine, and Key Pharmacometabolomics Platform of Chinese Medicines, Heping Road 24, Harbin, 150040, China

    Aihua Zhang, Hui Sun, Wejun Sun, Yuan Ye & Xijun Wang

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  1. Aihua Zhang
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  2. Hui Sun
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  3. Wejun Sun
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  4. Yuan Ye
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  5. Xijun Wang
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Correspondence to Xijun Wang.

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Zhang, A., Sun, H., Sun, W. et al. Proteomic Identification Network Analysis of Haptoglobin as a Key Regulator Associated with Liver Fibrosis. Appl Biochem Biotechnol 169, 832–846 (2013). https://doi.org/10.1007/s12010-012-0001-5

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  • DOI: https://doi.org/10.1007/s12010-012-0001-5

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