{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:07:03Z","timestamp":1760234823524,"version":"build-2065373602"},"reference-count":30,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,6,18]],"date-time":"2021-06-18T00:00:00Z","timestamp":1623974400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["MOST 107-2314-B-038-089"],"award-info":[{"award-number":["MOST 107-2314-B-038-089"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ministry of Education of Taiwan","award":["DP2-107-21121-T-01"],"award-info":[{"award-number":["DP2-107-21121-T-01"]}]},{"DOI":"10.13039\/501100010613","name":"Taipei Medical University Hospital","doi-asserted-by":"publisher","award":["107IIT06"],"award-info":[{"award-number":["107IIT06"]}],"id":[{"id":"10.13039\/501100010613","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Mackay Junior College of Medicine, Nursing, and Management","award":["MKC108R02"],"award-info":[{"award-number":["MKC108R02"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>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\u2212stimulated human PMCs and intrapleural doxycycline\u2212injected 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 &gt; 10 mm (n = 26) than those without (n = 38), and had positive correlation with pleural fibrosis shadowing. CBHA significantly reduced LTA\u2212induced PAI-1 and collagen expression via inhibition of JNK, and decreased PAI-1 promoter activity and mRNA levels in PMCs. Furthermore, in doxycycline\u2212treated rats, CBHA substantially repressed PAI-1 and collagen synthesis in pleural mesothelium and minimized pleural fibrosis. Conclusively, CBHA abrogates LTA\u2212induced PAI-1 and collagen expression in PMCs and attenuates experimental pleural fibrosis. PAI-1 inhibition by HDACi may confer potential therapy for pleural fibrosis.<\/jats:p>","DOI":"10.3390\/ph14060585","type":"journal-article","created":{"date-parts":[[2021,6,18]],"date-time":"2021-06-18T11:19:20Z","timestamp":1624015160000},"page":"585","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["HDAC Inhibitor Abrogates LTA\u2212Induced PAI-1 Expression in Pleural Mesothelial Cells and Attenuates Experimental Pleural Fibrosis"],"prefix":"10.3390","volume":"14","author":[{"given":"Wei-Lin","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Nursing, MacKay Junior College of Medicine, Nursing, and Management, Taipei 112, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mei-Chuan","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Medicine, Department of Internal Medicine, Taipei Medical University Hospital, Taipei 110, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shang-Fu","family":"Hsu","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Medicine, Department of Internal Medicine, Taipei Medical University Hospital, Taipei 110, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shih-Hsin","family":"Hsiao","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Medicine, Department of Internal Medicine, Taipei Medical University Hospital, Taipei 110, Taiwan"},{"name":"Division of Pulmonary Medicine, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0656-976X","authenticated-orcid":false,"given":"Chi-Li","family":"Chung","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Medicine, Department of Internal Medicine, Taipei Medical University Hospital, Taipei 110, Taiwan"},{"name":"Division of Pulmonary Medicine, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"},{"name":"School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1111\/j.1440-1843.2003.00539.x","article-title":"Pathogenesis of pleural infection","volume":"9","author":"Hage","year":"2004","journal-title":"Respirology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.ccm.2005.12.003","article-title":"Pleural fibrosis","volume":"27","author":"Jantz","year":"2006","journal-title":"Clin. 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