دورية أكاديمية
Therapeutic targets in lung tissue remodelling and fibrosis.
| العنوان: | Therapeutic targets in lung tissue remodelling and fibrosis. |
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| المؤلفون: | Liu G; Centre for Inflammation, Centenary Institute and University of Technology Sydney, Sydney, NSW, Australia., Philp AM; Centre for Inflammation, Centenary Institute and University of Technology Sydney, Sydney, NSW, Australia; St Vincent's Medical School, UNSW Medicine, UNSW, Sydney, NSW, Australia., Corte T; Royal Prince Alfred Hospital, Camperdown, NSW, Australia; Sydney Medical School, University of Sydney, Sydney, NSW, Australia., Travis MA; The Lydia Becker Institute of Immunology and Inflammation, Faculty of Biology, Medicine and Health, Manchester Academic Health Sciences Centre and Wellcome Trust Centre for Cell-Matrix Research, University of Manchester, Manchester, United Kingdom., Schilter H; Pharmaxis Ltd, 20 Rodborough Road, Frenchs Forest, Sydney, NSW, Australia., Hansbro NG; Centre for Inflammation, Centenary Institute and University of Technology Sydney, Sydney, NSW, Australia., Burns CJ; Walter and Eliza Hall Institute of Medical Research, Department of Medical Biology, The University of Melbourne, Melbourne, VIC 3010, Australia., Eapen MS; Respiratory Translational Research Group, Department of Laboratory Medicine, School of Health Sciences, University of Tasmania, Launceston, TAS, Australia., Sohal SS; Respiratory Translational Research Group, Department of Laboratory Medicine, School of Health Sciences, University of Tasmania, Launceston, TAS, Australia., Burgess JK; University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), Department of Pathology and Medical Biology, Groningen, The Netherlands; Woolcock Institute of Medical Research, Discipline of Pharmacology, The University of Sydney, Sydney, NSW, Australia., Hansbro PM; Centre for Inflammation, Centenary Institute and University of Technology Sydney, Sydney, NSW, Australia. Electronic address: Philip.Hansbro@uts.edu.au. |
| المصدر: | Pharmacology & therapeutics [Pharmacol Ther] 2021 Sep; Vol. 225, pp. 107839. Date of Electronic Publication: 2021 Mar 25. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't; Review |
| اللغة: | English |
| بيانات الدورية: | Publisher: Pergamon Press Country of Publication: England NLM ID: 7905840 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-016X (Electronic) Linking ISSN: 01637258 NLM ISO Abbreviation: Pharmacol Ther Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Oxford, Elmsford, N. Y., Pergamon Press. |
| مواضيع طبية MeSH: | Lung Diseases/*drug therapy , Lung Diseases/*physiopathology, Airway Remodeling/physiology ; Asthma/drug therapy ; Asthma/physiopathology ; Calcium-Binding Proteins/metabolism ; Extracellular Matrix/metabolism ; Fibroblasts ; Fibrosis/physiopathology ; Glycoproteins/metabolism ; Humans ; Idiopathic Pulmonary Fibrosis/drug therapy ; Idiopathic Pulmonary Fibrosis/physiopathology ; Matrix Metalloproteinases/metabolism ; Pulmonary Disease, Chronic Obstructive/drug therapy ; Pulmonary Disease, Chronic Obstructive/physiopathology ; Transforming Growth Factor beta |
| مستخلص: | Structural changes involving tissue remodelling and fibrosis are major features of many pulmonary diseases, including asthma, chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). Abnormal deposition of extracellular matrix (ECM) proteins is a key factor in the development of tissue remodelling that results in symptoms and impaired lung function in these diseases. Tissue remodelling in the lungs is complex and differs between compartments. Some pathways are common but tissue remodelling around the airways and in the parenchyma have different morphologies. Hence it is critical to evaluate both common fibrotic pathways and those that are specific to different compartments; thereby expanding the understanding of the pathogenesis of fibrosis and remodelling in the airways and parenchyma in asthma, COPD and IPF with a view to developing therapeutic strategies for each. Here we review the current understanding of remodelling features and underlying mechanisms in these major respiratory diseases. The differences and similarities of remodelling are used to highlight potential common therapeutic targets and strategies. One central pathway in remodelling processes involves transforming growth factor (TGF)-β induced fibroblast activation and myofibroblast differentiation that increases ECM production. The current treatments and clinical trials targeting remodelling are described, as well as potential future directions. These endeavours are indicative of the renewed effort and optimism for drug discovery targeting tissue remodelling and fibrosis. Competing Interests: Declaration of Competing Interest T.C. reports grants and/or personal fees from Boehringer Ingelheim, Roche, Gilead, Bayer, Intermune, AstraZeneca, BMS, Promedior, Ad Alta. C.J.B is a director and shareholder of Amplia Therapeutics, developing anti-fibrotic drugs for the treatment of IPF. P.M.H. has received funding from Pharmaxis for the study of LOX2 inhibitors, and is on the Scientific Advisory Board of Amplia Therapeutics. J.K.B has received research funding from Boehringer Ingelheim. Other authors declare that there are no conflicts of interest. (Copyright © 2021 Elsevier Inc. All rights reserved.) |
| معلومات مُعتمدة: | MR/V011243/1 United Kingdom MRC_ Medical Research Council |
| فهرسة مساهمة: | Keywords: Asthma; COPD; COVID-19; Collagen; Extracellular matrix; Fibroblasts; Fibrosis; IPF; Remodelling |
| المشرفين على المادة: | 0 (Calcium-Binding Proteins) 0 (Glycoproteins) 0 (Transforming Growth Factor beta) 0 (fibulin) EC 3.4.24.- (Matrix Metalloproteinases) |
| تواريخ الأحداث: | Date Created: 20210328 Date Completed: 20210721 Latest Revision: 20220324 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1016/j.pharmthera.2021.107839 |
| PMID: | 33774068 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1879-016X |
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| DOI: | 10.1016/j.pharmthera.2021.107839 |