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Article

HDAC Inhibitor Abrogates LTA−Induced PAI-1 Expression in Pleural Mesothelial Cells and Attenuates Experimental Pleural Fibrosis

by 1,†, 2,†, 2, 2,3,* and 2,3,4,*
1
Department of Nursing, MacKay Junior College of Medicine, Nursing, and Management, Taipei 112, Taiwan
2
Division of Pulmonary Medicine, Department of Internal Medicine, Taipei Medical University Hospital, Taipei 110, Taiwan
3
Division of Pulmonary Medicine, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
4
School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Nektarios Barabutis
Pharmaceuticals 2021, 14(6), 585; https://0-doi-org.brum.beds.ac.uk/10.3390/ph14060585
Received: 1 June 2021 / Revised: 15 June 2021 / Accepted: 16 June 2021 / Published: 18 June 2021
(This article belongs to the Special Issue Lung Injury and Repair)
Lipoteichoic acid (LTA) stimulates pleural mesothelial cell (PMC) to overproduce plasminogen activator inhibitor-1 (PAI-1), and thus may promote pleural fibrosis in Gram-positive bacteria (GPB) parapneumonic effusion (PPE). Histone deacetylase inhibitor (HDACi) was found to possess anti-fibrotic properties. However, the effects of HDACi on pleural fibrosis remain unclear. The effusion PAI-1 was measured among 64 patients with GPB PPE. Pleural fibrosis was measured as radiographical residual pleural thickening (RPT) and opacity at a 12-month follow-up. The LTA−stimulated human PMCs and intrapleural doxycycline−injected rats were pretreated with or without the pan-HDACi, m-carboxycinnamic acid bis-hydroxamide (CBHA), then PAI-1 and collagen expression and activated signalings in PMCs, and morphologic pleural changes in rats were measured. Effusion PAI-1 levels were significantly higher in GPB PPE patients with RPT > 10 mm (n = 26) than those without (n = 38), and had positive correlation with pleural fibrosis shadowing. CBHA significantly reduced LTA−induced PAI-1 and collagen expression via inhibition of JNK, and decreased PAI-1 promoter activity and mRNA levels in PMCs. Furthermore, in doxycycline−treated rats, CBHA substantially repressed PAI-1 and collagen synthesis in pleural mesothelium and minimized pleural fibrosis. Conclusively, CBHA abrogates LTA−induced PAI-1 and collagen expression in PMCs and attenuates experimental pleural fibrosis. PAI-1 inhibition by HDACi may confer potential therapy for pleural fibrosis. View Full-Text
Keywords: histone deacetylase inhibitor; lipoteichoic acid; plasminogen activator inhibitor-1; pleural fibrosis; pleural mesothelial cell; residual pleural thickening histone deacetylase inhibitor; lipoteichoic acid; plasminogen activator inhibitor-1; pleural fibrosis; pleural mesothelial cell; residual pleural thickening
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MDPI and ACS Style

Chen, W.-L.; Chen, M.-C.; Hsu, S.-F.; Hsiao, S.-H.; Chung, C.-L. HDAC Inhibitor Abrogates LTA−Induced PAI-1 Expression in Pleural Mesothelial Cells and Attenuates Experimental Pleural Fibrosis. Pharmaceuticals 2021, 14, 585. https://0-doi-org.brum.beds.ac.uk/10.3390/ph14060585

AMA Style

Chen W-L, Chen M-C, Hsu S-F, Hsiao S-H, Chung C-L. HDAC Inhibitor Abrogates LTA−Induced PAI-1 Expression in Pleural Mesothelial Cells and Attenuates Experimental Pleural Fibrosis. Pharmaceuticals. 2021; 14(6):585. https://0-doi-org.brum.beds.ac.uk/10.3390/ph14060585

Chicago/Turabian Style

Chen, Wei-Lin, Mei-Chuan Chen, Shang-Fu Hsu, Shih-Hsin Hsiao, and Chi-Li Chung. 2021. "HDAC Inhibitor Abrogates LTA−Induced PAI-1 Expression in Pleural Mesothelial Cells and Attenuates Experimental Pleural Fibrosis" Pharmaceuticals 14, no. 6: 585. https://0-doi-org.brum.beds.ac.uk/10.3390/ph14060585

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