ArticleScientific reports2016
SARS coronavirus papain-like protease induces Egr-1-dependent up-regulation of TGF-β1 via ROS/p38 MAPK/STAT3 pathway.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.
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Who cites it
81 citing papers in PubMed, 126 citations in OpenAlex.
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- Roles of Reactive Oxygen Species in Relationships Between Viral Infections and Alzheimer's Disease and Related Dementia.Antioxidants (Basel, Switzerland) · 2026Review
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- Contribution of the Activated mTOR-STAT3 Pathway to the Pathogenesis of Focal Cortical Dysplasia Type IIIa in Pediatric Patients through Astrocyte Proliferation Mediation.Current molecular medicine · 2025Article
- Interaction Network Characterization of Infectious Bronchitis Virus Nsp2 with Host Proteins.Veterinary sciences · 2024Article
- Anshen Shumai Decoction inhibits post-infarction inflammation and myocardial remodeling through suppression of the p38 MAPK/c-FOS/EGR1 pathway.Journal of molecular histology · 2024Article
- Differences in syncytia formation by SARS-CoV-2 variants modify host chromatin accessibility and cellular senescence via TP53.Cell reports · 2023Article
- Vimentin takes a hike - Emerging roles of extracellular vimentin in cancer and wound healing.Current opinion in cell biology · 2023Review
- Anticancer pan-ErbB inhibitors reduce inflammation and tissue injury and exert broad-spectrum antiviral effects.The Journal of clinical investigation · 2023Article
- Host Expression Profiling From Diagnostic Coronavirus Disease 2019 Swabs Associates Upper Respiratory Tract Immune Responses With Radiologic Lung Pathology and Clinical Severity.Open forum infectious diseases · 2023Article
- Dual domain recognition determines SARS-CoV-2 PLpro selectivity for human ISG15 and K48-linked di-ubiquitin.Nature communications · 2023Article
- Deciphering molecular mechanisms of SARS-CoV-2 pathogenesis and drug repurposing through GRN motifs: a comprehensive systems biology study.3 Biotech · 2023Article
- Dual domain recognition determines SARS-CoV-2 PLpro selectivity for human ISG15 and K48-linked di-ubiquitin.bioRxiv : the preprint server for biology · 2023Article
- Differential expression of antiviral and immune-related genes in individuals with COVID-19 asymptomatic or with mild symptoms.Frontiers in cellular and infection microbiology · 2023Article
- Pirfenidone and post-Covid-19 pulmonary fibrosis: invoked again for realistic goals.Inflammopharmacology · 2022Review
- Possible Role of Matrix Metalloproteinases and TGF-β in COVID-19 Severity and Sequelae.Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2022Review
- Extracellular Vimentin as a Target Against SARS-CoV-2 Host Cell Invasion.Small (Weinheim an der Bergstrasse, Germany) · 2022Article
- Examining the role of EGR1 during viral infections.Frontiers in microbiology · 2022Review
21 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
SARS coronavirus (SARS-CoV) papain-like protease (PLpro) has been identified in TGF-β1 up-regulation in human promonocytes (Proteomics 2012, 12: 3193-205). This study investigates the mechanisms of SARS-CoV PLpro-induced TGF-β1 promoter activation in human lung epithelial cells and mouse models. SARS-CoV PLpro dose- and time-dependently up-regulates TGF-β1 and vimentin in A549 cells. Dual luciferase reporter assays with TGF-β1 promoter plasmids indicated that TGF-β1 promoter region between -175 to -60, the Egr-1 binding site, was responsible for TGF-β1 promoter activation induced by SARS-CoV PLpro. Subcellular localization analysis of transcription factors showed PLpro triggering nuclear translocation of Egr-1, but not NF-κB and Sp-1. Meanwhile, Egr-1 silencing by siRNA significantly reduced PLpro-induced up-regulation of TGF-β1, TSP-1 and pro-fibrotic genes. Furthermore, the inhibitors for ROS (YCG063), p38 MAPK (SB203580), and STAT3 (Stattic) revealed ROS/p38 MAPK/STAT3 pathway involving in Egr-1 dependent activation of TGF-β1 promoter induced by PLpro. In a mouse model with a direct pulmonary injection, PLpro stimulated macrophage infiltration into lung, up-regulating Egr-1, TSP-1, TGF-β1 and vimentin expression in lung tissues. The results revealed that SARS-CoV PLpro significantly triggered Egr-1 dependent activation of TGF-β1 promoter via ROS/p38 MAPK/STAT3 pathway, correlating with up-regulation of pro-fibrotic responses in vitro and in vivo.
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