SARS coronavirus papain-like protease up-regulates the collagen expression through non-Samd TGF-β1 signaling.

Abstract:

:SARS coronavirus (CoV) papain-like protease (PLpro) reportedly induced the production of TGF-β1 through p38 MAPK/STAT3-meidated Egr-1-dependent activation (Sci. Rep. 6, 25754). This study investigated the correlation of PLpro-induced TGF-β1 with the expression of Type I collagen in human lung epithelial cells and mouse pulmonary tissues. Specific inhibitors for TGF-βRI, p38 MAPK, MEK, and STAT3 proved that SARS-CoV PLpro induced TGF-β1-dependent up-regulation of Type I collagen in vitro and in vivo. Subcellular localization analysis of SMAD3 and SMAD7 indicated that non-SMAD pathways in TGF-β1 signaling involved in the production of Type I collagen in transfected cells with pSARS-PLpro. Comprehensive analysis of ubiquitin-conjugated proteins using immunoprecipitation and nanoLC-MS/MS indicated that SARS-CoV PLpro caused the change in the ubiquitination profile of Rho GTPase family proteins, in which linked with the increase of Rho-like GTPase family proteins. Moreover, selective inhibitors TGF-βRI and STAT6 (AS1517499) ascertained that STAT6 activation was required for PLpro-induced TGF-β1-dependent up-regulation of Type I collagen in human lung epithelial cells. The results showed that SARS-CoV PLpro stimulated TGF-β1-dependent expression of Type I collagen via activating STAT6 pathway.

journal_name

Virus Res

journal_title

Virus research

authors

Wang CY,Lu CY,Li SW,Lai CC,Hua CH,Huang SH,Lin YJ,Hour MJ,Lin CW

doi

10.1016/j.virusres.2017.04.008

subject

Has Abstract

pub_date

2017-05-02 00:00:00

pages

58-66

eissn

0168-1702

issn

1872-7492

pii

S0168-1702(17)30034-5

journal_volume

235

pub_type

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