Thrombin Upregulates PAI-1 and Mesothelial–Mesenchymal Transition Through PAR-1 and Contributes to Tuberculous Pleural Fibrosis
| العنوان: | Thrombin Upregulates PAI-1 and Mesothelial–Mesenchymal Transition Through PAR-1 and Contributes to Tuberculous Pleural Fibrosis |
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| المؤلفون: | Cheng Ying Hsieh, Joen Rong Sheu, Wei Lin Chen, Chih Hao Yang, Jie Heng Tsai, Chi Li Chung |
| المصدر: | International Journal of Molecular Sciences, Vol 20, Iss 20, p 5076 (2019) International Journal of Molecular Sciences Volume 20 Issue 20 |
| بيانات النشر: | MDPI AG, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, Mesoderm, lcsh:Chemistry, chemistry.chemical_compound, Mice, Phosphatidylinositol 3-Kinases, 0302 clinical medicine, lcsh:QH301-705.5, Spectroscopy, Aged, 80 and over, mesothelial–mesenchymal transition, biology, General Medicine, Exudates and Transudates, Middle Aged, respiratory system, thrombin, Computer Science Applications, Effusion, Plasminogen activator inhibitor-1, Pleura, plasminogen activator inhibitor-1, Female, pleural fibrosis, residual pleura thickening, medicine.drug, Signal Transduction, Adult, tuberculous pleural fibrosis, Catalysis, Article, Inorganic Chemistry, 03 medical and health sciences, Tissue factor, Young Adult, Thrombin, In vivo, Plasminogen Activator Inhibitor 1, medicine, Animals, Humans, Tuberculosis, Receptor, PAR-1, Physical and Theoretical Chemistry, tuberculous pleural effusion, Molecular Biology, Aged, business.industry, Organic Chemistry, Mycobacterium tuberculosis, Fibrosis, In vitro, respiratory tract diseases, Fibronectin, Mice, Inbred C57BL, Pleural Effusion, Disease Models, Animal, pleural mesothelial cell, 030104 developmental biology, 030228 respiratory system, chemistry, lcsh:Biology (General), lcsh:QD1-999, biology.protein, Cancer research, business, Plasminogen activator, Follow-Up Studies |
| الوصف: | Thrombin is an essential procoagulant and profibrotic mediator. However, its implication in tuberculous pleural effusion (TBPE) remains unknown. The effusion thrombin and plasminogen activator inhibitor-1 (PAI-1) levels were measured among transudative pleural effusion (TPE, n = 22) and TBPE (n = 24) patients. Pleural fibrosis, identified as radiological residual pleural thickening (RPT) and shadowing, was measured at 12-month follow-up. Moreover, in vivo and in vitro effects of thrombin on PAI-1 expression and mesothelial&ndash mesenchymal transition (MMT) were assessed. We demonstrated the effusion thrombin levels were significantly higher in TBPE than TPE, especially greater in TBPE patients with RPT > 10mm than those without, and correlated positively with PAI-1 and pleural fibrosis area. In carbon black/bleomycin-treated mice, knockdown of protease-activated receptor-1 (PAR-1) markedly downregulated &alpha smooth muscle actin (&alpha SMA) and fibronectin, and attenuated pleural fibrosis. In pleural mesothelial cells (PMCs), thrombin concentration-dependently increased PAI-1, &alpha SMA, and collagen I expression. Specifically, Mycobacterium tuberculosis H37Ra (MTBRa) induced thrombin production by PMCs via upregulating tissue factor and prothrombin, and PAR-1 silencing considerably abrogated MTBRa&minus stimulated PAI-1 expression and MMT. Consistently, prothrombin/PAR-1 expression was evident in the pleural mesothelium of TBPE patients. Conclusively, thrombin upregulates PAI-1 and MMT and may contribute to tuberculous pleural fibrosis. Thrombin/PAR-1 inhibition may confer potential therapy for pleural fibrosis. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1422-0067 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::898ef521247c15109b0023fa414edec8Test https://www.mdpi.com/1422-0067/20/20/5076Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....898ef521247c15109b0023fa414edec8 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14220067 |
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