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

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

Auteurs : Shih-Wen Li ; Tsuey-Ching Yang ; Lei Wan ; Ying-Ju Lin ; Fuu-Jen Tsai ; Chien-Chen Lai ; Cheng-Wen Lin

Source :

Proteomics [ 1615-9853 ] ; 2012.

RBID : PMC:7168038

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.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7168038

DOI: 10.1002/pmic.201200225
PubMed: NONE
PubMed Central: 7168038

Affiliations:

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PMC:7168038

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<front><div type="abstract" xml:lang="en"><p>Severe acute respiratory syndrome (<styled-content style="fixed-case" toggle="no">SARS</styled-content>
) coronavirus (<styled-content style="fixed-case" toggle="no">SARS</styled-content>
‐<styled-content style="fixed-case" toggle="no">C</styled-content>
o<styled-content style="fixed-case" toggle="no">V</styled-content>
) papain‐like protease (<styled-content style="fixed-case" toggle="no">PL</styled-content>
pro), a deubiquitinating enzyme, demonstrates inactivation of interferon (<styled-content style="fixed-case" toggle="no">IFN</styled-content>
) regulatory factor 3 and <styled-content style="fixed-case" toggle="no">NF</styled-content>
‐κ<styled-content style="fixed-case" toggle="no">B</styled-content>
, reduction of IFN induction, and suppression of type I <styled-content style="fixed-case" toggle="no">IFN</styled-content>
 signaling pathway. This study investigates cytokine expression and proteomic change induced by <styled-content style="fixed-case" toggle="no">SARS</styled-content>
‐<styled-content style="fixed-case" toggle="no">C</styled-content>
o<styled-content style="fixed-case" toggle="no">V PL</styled-content>
pro in human promonocyte cells. PLpro significantly increased <styled-content style="fixed-case" toggle="no">TGF</styled-content>
‐β1 m<styled-content style="fixed-case" toggle="no">RNA</styled-content>
 expression (greater than fourfold) and protein production (greater than threefold). Proteomic analysis, <styled-content style="fixed-case" toggle="no">W</styled-content>
estern blot, and quantitative real‐time <styled-content style="fixed-case" toggle="no">PCR</styled-content>
 assays indicated <styled-content style="fixed-case" toggle="no">PL</styled-content>
pro upregulating <styled-content style="fixed-case" toggle="no">TGF</styled-content>
‐β1‐associated genes: <styled-content style="fixed-case" toggle="no">HSP</styled-content>
27, protein disulfide isomerase <styled-content style="fixed-case" toggle="no">A</styled-content>
3 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 <styled-content style="fixed-case" toggle="no">E</styled-content>
2–25k and proteasome subunit alpha type 5. Proteasome inhibitor <styled-content style="fixed-case" toggle="no">MG</styled-content>
‐132 significantly reduced expression of <styled-content style="fixed-case" toggle="no">TGF</styled-content>
‐β1 and vimentin. <styled-content style="fixed-case" toggle="no">PL</styled-content>
pro upregulated <styled-content style="fixed-case" toggle="no">HSP</styled-content>
27, linking with activation of p38 <styled-content style="fixed-case" toggle="no">MAPK</styled-content>
 and <styled-content style="fixed-case" toggle="no">ERK</styled-content>
1/2 signaling. Treatment with <styled-content style="fixed-case" toggle="no">SB</styled-content>
203580 and <styled-content style="fixed-case" toggle="no">U</styled-content>
0126 reduced <styled-content style="fixed-case" toggle="no">PL</styled-content>
pro‐induced expression of <styled-content style="fixed-case" toggle="no">TGF</styled-content>
‐β1, vimentin, and type I collagen. Results point to <styled-content style="fixed-case" toggle="no">SARS</styled-content>
‐<styled-content style="fixed-case" toggle="no">C</styled-content>
o<styled-content style="fixed-case" toggle="no">V PL</styled-content>
pro triggering <styled-content style="fixed-case" toggle="no">TGF</styled-content>
‐β1 production via ubiquitin proteasome, p38 <styled-content style="fixed-case" toggle="no">MAPK</styled-content>
, and <styled-content style="fixed-case" toggle="no">ERK</styled-content>
1/2‐mediated signaling.</p>
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<name sortKey="Li, Shih En" sort="Li, Shih En" uniqKey="Li S" first="Shih-Wen" last="Li">Shih-Wen Li</name>
<name sortKey="Lin, Cheng En" sort="Lin, Cheng En" uniqKey="Lin C" first="Cheng-Wen" last="Lin">Cheng-Wen Lin</name>
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Correlation between TGF‐β1 expression and proteomic profiling induced by severe acute respiratory syndrome coronavirus papain‐like protease

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

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