Characterization of Fibrinogen as a Key Modulator in Patients with Wilson's Diseases with Functional Proteomic Tools

Pei Wen Wang, Tung Yi Lin, Yu Chiang Hung, Wen Neng Chang, Pei Ming Yang, Mu Hong Chen, Chau Ting Yeh, Tai Long Pan

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    2 引文 斯高帕斯(Scopus)


    Wilson's disease (WD) is an autosomal recessive disorder of copper metabolism caused by defects in the ATPase gene (ATP7B). The various clinical features result from the massive accumulation of copper in the liver, cornea and basal ganglia. Although WD can be effectively treated with proper medicine, this disease is difficult to clearly diagnose due to its indefinite symptoms. In the current study, we achieved a positive correlation between clinical symptoms and the enzymatic activity of ceruloplasmin in WD patients. Furthermore, proteome profiles of plasma as well as network analysis demonstrated that fibrinogen is a critical indicator which is significantly unregulated in WD subjects in comparison to healthy donors and closely linked to pathogenesis of WD. Here, we applied 2DE-immunoblots and immunohistochemistry to verify the protein level and localization in situ. The enhanced expression of fibrinogen in the plasma of WD subjects with respect to that of healthy controls and patients with distinct disorders was also confirmed by utilizing clinical samples. As expected, application of high dose of copper induced expression of fibrinogen, while knockdown of ceruloplasmin also resulted in upregulation of fibrinogen as well as elimination of superoxide dismutase (SOD), leading to increased oxidative stress in cells. In summary, the liver injury or oxidative stress induced by the progression of WD may account for the obvious increase of fibrinogen, which in turn triggers inflammatory responses and interferes coagulation cascades; this finding sheds light on the early detection and diagnosis of WD.

    期刊International Journal of Molecular Sciences
    出版狀態已發佈 - 9月 12 2019

    ASJC Scopus subject areas

    • 催化
    • 分子生物學
    • 光譜
    • 電腦科學應用
    • 物理與理論化學
    • 有機化學
    • 無機化學


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