HDAC Inhibitor Abrogates LTA−Induced PAI-1 Expression in Pleural Mesothelial Cells and Attenuates Experimental Pleural Fibrosis
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 pro...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-06-01
|
| Series: | Pharmaceuticals |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1424-8247/14/6/585 |
| _version_ | 1797529615384707072 |
|---|---|
| author | Wei-Lin Chen Mei-Chuan Chen Shang-Fu Hsu Shih-Hsin Hsiao Chi-Li Chung |
| author_facet | Wei-Lin Chen Mei-Chuan Chen Shang-Fu Hsu Shih-Hsin Hsiao Chi-Li Chung |
| author_sort | Wei-Lin Chen |
| collection | DOAJ |
| description | 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 (<i>n</i> = 26) than those without (<i>n</i> = 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. |
| first_indexed | 2024-03-10T10:17:17Z |
| format | Article |
| id | doaj.art-1c877b07864942b296bc3ac9c025b719 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-10T10:17:17Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-1c877b07864942b296bc3ac9c025b7192023-11-22T00:43:21ZengMDPI AGPharmaceuticals1424-82472021-06-0114658510.3390/ph14060585HDAC Inhibitor Abrogates LTA−Induced PAI-1 Expression in Pleural Mesothelial Cells and Attenuates Experimental Pleural FibrosisWei-Lin Chen0Mei-Chuan Chen1Shang-Fu Hsu2Shih-Hsin Hsiao3Chi-Li Chung4Department of Nursing, MacKay Junior College of Medicine, Nursing, and Management, Taipei 112, TaiwanDivision of Pulmonary Medicine, Department of Internal Medicine, Taipei Medical University Hospital, Taipei 110, TaiwanDivision of Pulmonary Medicine, Department of Internal Medicine, Taipei Medical University Hospital, Taipei 110, TaiwanDivision of Pulmonary Medicine, Department of Internal Medicine, Taipei Medical University Hospital, Taipei 110, TaiwanDivision of Pulmonary Medicine, Department of Internal Medicine, Taipei Medical University Hospital, Taipei 110, TaiwanLipoteichoic 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 (<i>n</i> = 26) than those without (<i>n</i> = 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.https://www.mdpi.com/1424-8247/14/6/585histone deacetylase inhibitorlipoteichoic acidplasminogen activator inhibitor-1pleural fibrosispleural mesothelial cellresidual pleural thickening |
| spellingShingle | Wei-Lin Chen Mei-Chuan Chen Shang-Fu Hsu Shih-Hsin Hsiao Chi-Li Chung HDAC Inhibitor Abrogates LTA−Induced PAI-1 Expression in Pleural Mesothelial Cells and Attenuates Experimental Pleural Fibrosis Pharmaceuticals histone deacetylase inhibitor lipoteichoic acid plasminogen activator inhibitor-1 pleural fibrosis pleural mesothelial cell residual pleural thickening |
| title | HDAC Inhibitor Abrogates LTA−Induced PAI-1 Expression in Pleural Mesothelial Cells and Attenuates Experimental Pleural Fibrosis |
| title_full | HDAC Inhibitor Abrogates LTA−Induced PAI-1 Expression in Pleural Mesothelial Cells and Attenuates Experimental Pleural Fibrosis |
| title_fullStr | HDAC Inhibitor Abrogates LTA−Induced PAI-1 Expression in Pleural Mesothelial Cells and Attenuates Experimental Pleural Fibrosis |
| title_full_unstemmed | HDAC Inhibitor Abrogates LTA−Induced PAI-1 Expression in Pleural Mesothelial Cells and Attenuates Experimental Pleural Fibrosis |
| title_short | HDAC Inhibitor Abrogates LTA−Induced PAI-1 Expression in Pleural Mesothelial Cells and Attenuates Experimental Pleural Fibrosis |
| title_sort | hdac inhibitor abrogates lta induced pai 1 expression in pleural mesothelial cells and attenuates experimental pleural fibrosis |
| topic | histone deacetylase inhibitor lipoteichoic acid plasminogen activator inhibitor-1 pleural fibrosis pleural mesothelial cell residual pleural thickening |
| url | https://www.mdpi.com/1424-8247/14/6/585 |
| work_keys_str_mv | AT weilinchen hdacinhibitorabrogatesltainducedpai1expressioninpleuralmesothelialcellsandattenuatesexperimentalpleuralfibrosis AT meichuanchen hdacinhibitorabrogatesltainducedpai1expressioninpleuralmesothelialcellsandattenuatesexperimentalpleuralfibrosis AT shangfuhsu hdacinhibitorabrogatesltainducedpai1expressioninpleuralmesothelialcellsandattenuatesexperimentalpleuralfibrosis AT shihhsinhsiao hdacinhibitorabrogatesltainducedpai1expressioninpleuralmesothelialcellsandattenuatesexperimentalpleuralfibrosis AT chilichung hdacinhibitorabrogatesltainducedpai1expressioninpleuralmesothelialcellsandattenuatesexperimentalpleuralfibrosis |