Correlation between TGF-β1 expression and proteomic profiling induced by severe acute respiratory syndrome coronavirus papain-like protease

Authors

  • Shih-Wen Li,

    1. Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung, Taiwan
    2. Institute of Molecular Biology, National Chung Hsing University, Taichung, Taiwan
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  • Tsuey-Ching Yang,

    1. Department of Biotechnology and Laboratory Science in Medicine, National Yang Ming University, Taipei, Taiwan
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  • Lei Wan,

    1. Department of Medical Genetics and Medical Research, China Medical University Hospital, Taichung, Taiwan
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  • Ying-Ju Lin,

    1. Department of Medical Genetics and Medical Research, China Medical University Hospital, Taichung, Taiwan
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  • Fuu-Jen Tsai,

    1. Department of Medical Genetics and Medical Research, China Medical University Hospital, Taichung, Taiwan
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  • Chien-Chen Lai,

    Corresponding author
    1. Department of Medical Genetics and Medical Research, China Medical University Hospital, Taichung, Taiwan
    • Institute of Molecular Biology, National Chung Hsing University, Taichung, Taiwan
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  • Cheng-Wen Lin

    Corresponding author
    1. Clinical Virology Laboratory, Department of Laboratory Medicine, China Medical University Hospital, Taichung, Taiwan
    2. Department of Biotechnology, Asia University, Taichung, Taiwan
    • Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung, Taiwan
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  • Colour Online: See the article online to view Figures 1, 4, and 8 in colour.

Correspondence: Prof. Dr. Cheng-Wen Lin, Department of Medical Laboratory Science and Biotechnology, China Medical University, No. 91, Hsueh-Shih Road, Taichung 404, Taiwan

E-mail: cwlin@mail.cmu.edu.tw

Fax: 886-4-22057414

Additional corresponding author: Professor Chien-Chen Lai

E-mail: lailai@dragon.nchu.edu.tw

Abstract

Severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) papain-like protease (PLpro), a deubiquitinating enzyme, demonstrates inactivation of interferon (IFN) regulatory factor 3 and NF-κB, reduction of IFN induction, and suppression of type I IFN signaling pathway. This study investigates cytokine expression and proteomic change induced by SARS-CoV PLpro in human promonocyte cells. PLpro significantly increased TGF-β1 mRNA expression (greater than fourfold) and protein production (greater than threefold). Proteomic analysis, Western blot, and quantitative real-time PCR assays indicated PLpro upregulating TGF-β1-associated genes: HSP27, protein disulfide isomerase A3 precursor, glial fibrillary acidic protein, vimentin, retinal dehydrogenase 2, and glutathione transferase omega-1. PLpro-activated ubiquitin proteasome pathway via upregulation of ubiquitin-conjugating enzyme E2–25k and proteasome subunit alpha type 5. Proteasome inhibitor MG-132 significantly reduced expression of TGF-β1 and vimentin. PLpro upregulated HSP27, linking with activation of p38 MAPK and ERK1/2 signaling. Treatment with SB203580 and U0126 reduced PLpro-induced expression of TGF-β1, vimentin, and type I collagen. Results point to SARS-CoV PLpro triggering TGF-β1 production via ubiquitin proteasome, p38 MAPK, and ERK1/2-mediated signaling.

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