Histone Deacetylase Inhibitor Impairs Plasminogen Activator Inhibitor-1 Expression via Inhibiting TNF-α-Activated MAPK/AP-1 Signaling Cascade.
In: BioMed Research International, Jg. 2014 (2014), S. 1-9
Online
academicJournal
Zugriff:
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. [ABSTRACT FROM AUTHOR]
Titel: |
Histone Deacetylase Inhibitor Impairs Plasminogen Activator Inhibitor-1 Expression via Inhibiting TNF-α-Activated MAPK/AP-1 Signaling Cascade.
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Autor/in / Beteiligte Person: | Chen, Wei-Lin ; Sheu, Joen-Rong ; Hsiao, Che-Jen ; Hsiao, Shih-Hsin ; Chung, Chi-Li ; Hsiao, George |
Link: | |
Zeitschrift: | BioMed Research International, Jg. 2014 (2014), S. 1-9 |
Veröffentlichung: | 2014 |
Medientyp: | academicJournal |
ISSN: | 2314-6133 (print) |
DOI: | 10.1155/2014/231012 |
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