{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:17:06Z","timestamp":1785428226607,"version":"3.56.0"},"reference-count":29,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"MacKay Junior College of Medicine, Nursing, and Management, Taiwan","award":["MKC 113R02"],"award-info":[{"award-number":["MKC 113R02"]}]},{"award":["MKC 113R02"],"award-info":[{"award-number":["MKC 113R02"]}],"id":[{"id":"https:\/\/ror.org\/03j9dwf95","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>High-mobility group box 1 (HMGB1) has been implicated in matrix remodeling and fibrotic disorders; however, its role in tuberculosis (TB)-associated pleural fibrosis remains unknown. Pleural fluid levels of HMGB1 and matrix metalloproteinase-1 (MMP-1) in patients with TB pleural effusion (TBPE, n = 36) or transudative pleural effusion (TPE, n = 14) were measured. The effects of Mycobacterium tuberculosis H37Ra (MTBRa) on HMGB1 and MMP-1 expression and their effects on mesothelial\u2013mesenchymal transition (MMT) in human pleural mesothelial cells (PMCs) were assessed. The levels of HMGB1 and MMP-1 were significantly higher in TBPE than in TPE. Elevated HMGB1 and MMP-1 levels in TBPE were positively correlated and both factors were significantly associated with post-TB residual pleural thickening (RPT), particularly in patients with RPT \u2265 10 mm. Colocalized expression of HMGB1 and MMP-1 was also observed in the pleural mesothelium of TBPE patients. MTBRa significantly induced HMGB1 expression in PMCs through activation of the JNK\/AP-1 signaling pathway, leading to MMT, enhanced collagen synthesis, and upregulation of MMP-1. Furthermore, silencing of MMP-1 markedly attenuated HMGB1-triggered MMT response. Collectively, HMGB1 promotes pleural fibrogenesis through JNK\/AP-1-dependent and MMP-1-mediated MMT, suggesting that targeting the HMGB1\/MMP-1 axis may represent a potential therapeutic strategy for TB-related pleural fibrosis.<\/jats:p>","DOI":"10.3390\/ijms27135961","type":"journal-article","created":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T14:51:25Z","timestamp":1783003885000},"page":"5961","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["HMGB1 Upregulates MMP-1-Mediated Mesothelial\u2013Mesenchymal Transition and Promotes Pleural Fibrosis in Tuberculous Pleural Effusion"],"prefix":"10.3390","volume":"27","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":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9597-1413","authenticated-orcid":false,"given":"Kai-Ling","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Medicine, Department of Internal Medicine, Taipei Medical University Hospital, Taipei 110, Taiwan"},{"name":"School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei-Chuan","family":"Chen","sequence":"additional","affiliation":[{"name":"Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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":[{"vocabulary":"crossref","role":"author"}]},{"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":"School of Respiratory Therapy, College of Medicine, Taipei Medical University, 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":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,2]]},"reference":[{"key":"ref_1","unstructured":"GBD 2021 Tuberculosis Collaborators (2024). 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