Abstract

Tumor necrosis factor-(TNF-)- α upregulates plasminogen activator inhibitor-(PAI-) 1 expression in pleural mesothelial cells (PMCs), contributing to fibrin deposition and pleural fibrosis. Histone deacetylases (HDACs) have been found implicated in fibrogenesis. However, the roles of TNF- α or HDAC in the regulation of PAI-1 expression have not been well investigated. We aimed to examine the effects and mechanisms of HDAC inhibition on TNF- α -induced PAI-1 expression in human PMCs. MeT-5A human PMCs were treated with TNF- α in the presence or absence of the m-carboxycinnamic acid bishydroxamide (CBHA), an HDAC class II inhibitor, and the HDAC activity, PAI-1 protein expression, mRNA, and activated signalings were analyzed. CBHA abrogated TNF- α -induced HDAC activity, PAI-1 protein and, mRNA expression in MeT-5A cells. Moreover, CBHA significantly enhanced mitogen-activated protein kinase phosphatase-(MKP-) 5/MKP-1 expression and inhibited p38/JNK activations, ATF2/c-Jun translocation, and PAI-1 promoter activity. Altogether, our data suggest that HDAC inhibition may abrogate TNF- α -activated MAPK/AP-1 signaling and PAI-1 expression in human PMCs. Given the antifibrotic effect through PAI-1 abrogation, CBHA may be utilized as a novel agent in the treatment of fibrotic diseases.

Original languageEnglish
Article number231012
JournalBioMed Research International
Volume2014
DOIs
Publication statusPublished - 2014

Fingerprint

Histone Deacetylase Inhibitors
Plasminogen Activator Inhibitor 1
Transcription Factor AP-1
Histone Deacetylases
Mitogen-Activated Protein Kinase Phosphatases
Plasminogen Inactivators
Messenger RNA
Fibrin
Proteins
Tumor Necrosis Factor-alpha
Chemical activation
Fibrosis
Up-Regulation
carboxycinnamic acid bishydroxamide

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Medicine(all)

Cite this

@article{9a0488a5920447428ebf637339c2231f,
title = "Histone deacetylase inhibitor impairs plasminogen activator inhibitor-1 expression via inhibiting TNF-α-activated MAPK/AP-1 signaling cascade",
abstract = "Tumor necrosis factor-(TNF-)- α upregulates plasminogen activator inhibitor-(PAI-) 1 expression in pleural mesothelial cells (PMCs), contributing to fibrin deposition and pleural fibrosis. Histone deacetylases (HDACs) have been found implicated in fibrogenesis. However, the roles of TNF- α or HDAC in the regulation of PAI-1 expression have not been well investigated. We aimed to examine the effects and mechanisms of HDAC inhibition on TNF- α -induced PAI-1 expression in human PMCs. MeT-5A human PMCs were treated with TNF- α in the presence or absence of the m-carboxycinnamic acid bishydroxamide (CBHA), an HDAC class II inhibitor, and the HDAC activity, PAI-1 protein expression, mRNA, and activated signalings were analyzed. CBHA abrogated TNF- α -induced HDAC activity, PAI-1 protein and, mRNA expression in MeT-5A cells. Moreover, CBHA significantly enhanced mitogen-activated protein kinase phosphatase-(MKP-) 5/MKP-1 expression and inhibited p38/JNK activations, ATF2/c-Jun translocation, and PAI-1 promoter activity. Altogether, our data suggest that HDAC inhibition may abrogate TNF- α -activated MAPK/AP-1 signaling and PAI-1 expression in human PMCs. Given the antifibrotic effect through PAI-1 abrogation, CBHA may be utilized as a novel agent in the treatment of fibrotic diseases.",
author = "Chen, {Wei Lin} and Sheu, {Joen Rong} and Hsiao, {Che Jen} and Hsiao, {Shih Hsin} and Chung, {Chi Li} and George Hsiao",
year = "2014",
doi = "10.1155/2014/231012",
language = "English",
volume = "2014",
journal = "BioMed Research International",
issn = "2314-6133",
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TY - JOUR

T1 - Histone deacetylase inhibitor impairs plasminogen activator inhibitor-1 expression via inhibiting TNF-α-activated MAPK/AP-1 signaling cascade

AU - Chen, Wei Lin

AU - Sheu, Joen Rong

AU - Hsiao, Che Jen

AU - Hsiao, Shih Hsin

AU - Chung, Chi Li

AU - Hsiao, George

PY - 2014

Y1 - 2014

N2 - Tumor necrosis factor-(TNF-)- α upregulates plasminogen activator inhibitor-(PAI-) 1 expression in pleural mesothelial cells (PMCs), contributing to fibrin deposition and pleural fibrosis. Histone deacetylases (HDACs) have been found implicated in fibrogenesis. However, the roles of TNF- α or HDAC in the regulation of PAI-1 expression have not been well investigated. We aimed to examine the effects and mechanisms of HDAC inhibition on TNF- α -induced PAI-1 expression in human PMCs. MeT-5A human PMCs were treated with TNF- α in the presence or absence of the m-carboxycinnamic acid bishydroxamide (CBHA), an HDAC class II inhibitor, and the HDAC activity, PAI-1 protein expression, mRNA, and activated signalings were analyzed. CBHA abrogated TNF- α -induced HDAC activity, PAI-1 protein and, mRNA expression in MeT-5A cells. Moreover, CBHA significantly enhanced mitogen-activated protein kinase phosphatase-(MKP-) 5/MKP-1 expression and inhibited p38/JNK activations, ATF2/c-Jun translocation, and PAI-1 promoter activity. Altogether, our data suggest that HDAC inhibition may abrogate TNF- α -activated MAPK/AP-1 signaling and PAI-1 expression in human PMCs. Given the antifibrotic effect through PAI-1 abrogation, CBHA may be utilized as a novel agent in the treatment of fibrotic diseases.

AB - Tumor necrosis factor-(TNF-)- α upregulates plasminogen activator inhibitor-(PAI-) 1 expression in pleural mesothelial cells (PMCs), contributing to fibrin deposition and pleural fibrosis. Histone deacetylases (HDACs) have been found implicated in fibrogenesis. However, the roles of TNF- α or HDAC in the regulation of PAI-1 expression have not been well investigated. We aimed to examine the effects and mechanisms of HDAC inhibition on TNF- α -induced PAI-1 expression in human PMCs. MeT-5A human PMCs were treated with TNF- α in the presence or absence of the m-carboxycinnamic acid bishydroxamide (CBHA), an HDAC class II inhibitor, and the HDAC activity, PAI-1 protein expression, mRNA, and activated signalings were analyzed. CBHA abrogated TNF- α -induced HDAC activity, PAI-1 protein and, mRNA expression in MeT-5A cells. Moreover, CBHA significantly enhanced mitogen-activated protein kinase phosphatase-(MKP-) 5/MKP-1 expression and inhibited p38/JNK activations, ATF2/c-Jun translocation, and PAI-1 promoter activity. Altogether, our data suggest that HDAC inhibition may abrogate TNF- α -activated MAPK/AP-1 signaling and PAI-1 expression in human PMCs. Given the antifibrotic effect through PAI-1 abrogation, CBHA may be utilized as a novel agent in the treatment of fibrotic diseases.

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