The dengue virus envelope protein induced PAI-1 gene expression via MEK/ERK pathways

Huey Wen Shyu, Yi Ying Lin, Lien Cheng Chen, Yi Fen Wang, Trai Ming Yeh, Shu Jem Su, Wei Cheng Cheng, Chang Yu Chen, Kuan Hua Lin, Miao Chen Chou

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Dengue virus (DV) infections cause mild dengue fever or severe life-threatening dengue haemorrhagic fever (DHF)/ dengue shock syndrome (DSS). DV-infected patients have high plasma concentrations of plasminogen activator inhibitor type I (PAI-1). However, the mechanism to cause haemorrhage in DV infections remains poorly understood. In this study, investigation was carried out on the purified recombinant domain III of the envelope glycoprotein of DV serotypes 2 (EIII) and the signalling pathways of EIII leading to PAI-1 gene expression were measured by RT-PCR, Western blot, and immunofluorescence stain. Reporter gene constructs containing serially 5'-deleted sequences of the proximal human PAI-1 promoter region were constructed and then transfected to Huh7 cells, a human hepatoma cell line, prior to EIII treatment. EIII increased the PAI-1 mRNA and protein levels in a dose-dependent manner in Huh7 cells. Results showed that U0126, an inhibitor of extracellular signal-regulated kinase (ERK) kinase (MEK), almost completely suppressed EIII-induced PAI-1 expression. The results suggest that the MEK/ERK signalling pathways mediate the EIII-dependent induction of PAI-1 gene expression via the proximal promoter region.

Original languageEnglish
Pages (from-to)1219-1227
Number of pages9
JournalThrombosis and Haemostasis
Volume104
Issue number6
DOIs
Publication statusPublished - 2010 Dec 1

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Viral Envelope Proteins
Dengue Virus
Plasminogen Activator Inhibitor 1
Mitogen-Activated Protein Kinase Kinases
Extracellular Signal-Regulated MAP Kinases
Severe Dengue
Gene Expression
Virus Diseases
Genetic Promoter Regions
MAP Kinase Kinase Kinases
Plasminogen Inactivators
Dengue
Reporter Genes
Fluorescent Antibody Technique
Hepatocellular Carcinoma
Coloring Agents
Western Blotting
Hemorrhage
Cell Line
Polymerase Chain Reaction

All Science Journal Classification (ASJC) codes

  • Hematology

Cite this

Shyu, H. W., Lin, Y. Y., Chen, L. C., Wang, Y. F., Yeh, T. M., Su, S. J., ... Chou, M. C. (2010). The dengue virus envelope protein induced PAI-1 gene expression via MEK/ERK pathways. Thrombosis and Haemostasis, 104(6), 1219-1227. https://doi.org/10.1160/TH10-05-0302
Shyu, Huey Wen ; Lin, Yi Ying ; Chen, Lien Cheng ; Wang, Yi Fen ; Yeh, Trai Ming ; Su, Shu Jem ; Cheng, Wei Cheng ; Chen, Chang Yu ; Lin, Kuan Hua ; Chou, Miao Chen. / The dengue virus envelope protein induced PAI-1 gene expression via MEK/ERK pathways. In: Thrombosis and Haemostasis. 2010 ; Vol. 104, No. 6. pp. 1219-1227.
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abstract = "Dengue virus (DV) infections cause mild dengue fever or severe life-threatening dengue haemorrhagic fever (DHF)/ dengue shock syndrome (DSS). DV-infected patients have high plasma concentrations of plasminogen activator inhibitor type I (PAI-1). However, the mechanism to cause haemorrhage in DV infections remains poorly understood. In this study, investigation was carried out on the purified recombinant domain III of the envelope glycoprotein of DV serotypes 2 (EIII) and the signalling pathways of EIII leading to PAI-1 gene expression were measured by RT-PCR, Western blot, and immunofluorescence stain. Reporter gene constructs containing serially 5'-deleted sequences of the proximal human PAI-1 promoter region were constructed and then transfected to Huh7 cells, a human hepatoma cell line, prior to EIII treatment. EIII increased the PAI-1 mRNA and protein levels in a dose-dependent manner in Huh7 cells. Results showed that U0126, an inhibitor of extracellular signal-regulated kinase (ERK) kinase (MEK), almost completely suppressed EIII-induced PAI-1 expression. The results suggest that the MEK/ERK signalling pathways mediate the EIII-dependent induction of PAI-1 gene expression via the proximal promoter region.",
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Shyu, HW, Lin, YY, Chen, LC, Wang, YF, Yeh, TM, Su, SJ, Cheng, WC, Chen, CY, Lin, KH & Chou, MC 2010, 'The dengue virus envelope protein induced PAI-1 gene expression via MEK/ERK pathways', Thrombosis and Haemostasis, vol. 104, no. 6, pp. 1219-1227. https://doi.org/10.1160/TH10-05-0302

The dengue virus envelope protein induced PAI-1 gene expression via MEK/ERK pathways. / Shyu, Huey Wen; Lin, Yi Ying; Chen, Lien Cheng; Wang, Yi Fen; Yeh, Trai Ming; Su, Shu Jem; Cheng, Wei Cheng; Chen, Chang Yu; Lin, Kuan Hua; Chou, Miao Chen.

In: Thrombosis and Haemostasis, Vol. 104, No. 6, 01.12.2010, p. 1219-1227.

Research output: Contribution to journalArticle

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T1 - The dengue virus envelope protein induced PAI-1 gene expression via MEK/ERK pathways

AU - Shyu, Huey Wen

AU - Lin, Yi Ying

AU - Chen, Lien Cheng

AU - Wang, Yi Fen

AU - Yeh, Trai Ming

AU - Su, Shu Jem

AU - Cheng, Wei Cheng

AU - Chen, Chang Yu

AU - Lin, Kuan Hua

AU - Chou, Miao Chen

PY - 2010/12/1

Y1 - 2010/12/1

N2 - Dengue virus (DV) infections cause mild dengue fever or severe life-threatening dengue haemorrhagic fever (DHF)/ dengue shock syndrome (DSS). DV-infected patients have high plasma concentrations of plasminogen activator inhibitor type I (PAI-1). However, the mechanism to cause haemorrhage in DV infections remains poorly understood. In this study, investigation was carried out on the purified recombinant domain III of the envelope glycoprotein of DV serotypes 2 (EIII) and the signalling pathways of EIII leading to PAI-1 gene expression were measured by RT-PCR, Western blot, and immunofluorescence stain. Reporter gene constructs containing serially 5'-deleted sequences of the proximal human PAI-1 promoter region were constructed and then transfected to Huh7 cells, a human hepatoma cell line, prior to EIII treatment. EIII increased the PAI-1 mRNA and protein levels in a dose-dependent manner in Huh7 cells. Results showed that U0126, an inhibitor of extracellular signal-regulated kinase (ERK) kinase (MEK), almost completely suppressed EIII-induced PAI-1 expression. The results suggest that the MEK/ERK signalling pathways mediate the EIII-dependent induction of PAI-1 gene expression via the proximal promoter region.

AB - Dengue virus (DV) infections cause mild dengue fever or severe life-threatening dengue haemorrhagic fever (DHF)/ dengue shock syndrome (DSS). DV-infected patients have high plasma concentrations of plasminogen activator inhibitor type I (PAI-1). However, the mechanism to cause haemorrhage in DV infections remains poorly understood. In this study, investigation was carried out on the purified recombinant domain III of the envelope glycoprotein of DV serotypes 2 (EIII) and the signalling pathways of EIII leading to PAI-1 gene expression were measured by RT-PCR, Western blot, and immunofluorescence stain. Reporter gene constructs containing serially 5'-deleted sequences of the proximal human PAI-1 promoter region were constructed and then transfected to Huh7 cells, a human hepatoma cell line, prior to EIII treatment. EIII increased the PAI-1 mRNA and protein levels in a dose-dependent manner in Huh7 cells. Results showed that U0126, an inhibitor of extracellular signal-regulated kinase (ERK) kinase (MEK), almost completely suppressed EIII-induced PAI-1 expression. The results suggest that the MEK/ERK signalling pathways mediate the EIII-dependent induction of PAI-1 gene expression via the proximal promoter region.

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