title: Correlation between TGF-β1 expression and proteomic profiling induced by severe acute respiratory syndrome coronavirus papain-like protease.
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.
authors.affiliation: Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung, Taiwan; Institute of Molecular Biology, National Chung Hsing University, Taichung, Taiwan.
authors.forename: Shih-Wen
authors.initials: SW
authors.lastname: Li
authors.forename: Tsuey-Ching
authors.initials: TC
authors.lastname: Yang
authors.forename: Lei
authors.initials: L
authors.lastname: Wan
authors.forename: Ying-Ju
authors.initials: YJ
authors.lastname: Lin
authors.forename: Fuu-Jen
authors.initials: FJ
authors.lastname: Tsai
authors.forename: Chien-Chen
authors.initials: CC
authors.lastname: Lai
authors.forename: Cheng-Wen
authors.initials: CW
authors.lastname: Lin
mesh_terms: D000818:Animals; D002460:Cell Line; D016009:Chi-Square Distribution; D000086782:Coronavirus 3C Proteases; D003546:Cysteine Endopeptidases / Q000494:pharmacology*; D015180:Electrophoresis, Gel, Two-Dimensional; D054884:Host-Pathogen Interactions; D006801:Humans; D007976:Leupeptins / Q000494:pharmacology; D051379:Mice; D055017:Monocyte-Macrophage Precursor Cells / Q000187:drug effects; D046988:Proteasome Endopeptidase Complex / Q000187:drug effects / Q000378:metabolism; D020543:Proteome / Q000187:drug effects*; D040901:Proteomics / Q000379:methods; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism; D014746:Vimentin / Q000378:metabolism; D014764:Viral Proteins / Q000494:pharmacology*
chemical_list: D007976:Leupeptins; D020543:Proteome; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D025801:Ubiquitin; D014746:Vimentin; D014764:Viral Proteins; D003546:Cysteine Endopeptidases; D000086782:Coronavirus 3C Proteases; D046988:Proteasome Endopeptidase Complex; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde