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Therapeutic targets in lung tissue remodelling and fibrosis

Liu, G, Philp, AM, Corte, T, Travis, MA, Schilter, H, Hansbro, NG, Burns, CJ, Eapen, MS ORCID: 0000-0003-0570-7059, Sohal, SS ORCID: 0000-0001-9627-6498, Burgess, JK and Hansbro, PM 2021 , 'Therapeutic targets in lung tissue remodelling and fibrosis' , Pharmacology and Therapeutics, vol. 225 , pp. 1-34 , doi: 10.1016/j.pharmthera.2021.107839.

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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 remodellingthat results in symptoms and impaired lung function in these diseases. Tissue remodelling in the lungs is complexand differs between compartments. Some pathways are common but tissue remodelling around the airways andin the parenchyma have different morphologies. Hence it is critical to evaluate both common fibrotic pathwaysand those that are specific to different compartments; thereby expanding the understanding of the pathogenesisof fibrosis and remodelling in the airways and parenchyma in asthma, COPD and IPF with a view to developingtherapeutic 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 tohighlight potential common therapeutic targets and strategies. One central pathway in remodelling processes involves transforming growth factor (TGF)-β induced fibroblast activation and myofibroblast differentiation thatincreases ECM production. The current treatments and clinical trials targeting remodelling are described, aswell as potential future directions. These endeavours are indicative of the renewed effort and optimism fordrug discovery targeting tissue remodelling and fibrosis.

Item Type: Article
Authors/Creators:Liu, G and Philp, AM and Corte, T and Travis, MA and Schilter, H and Hansbro, NG and Burns, CJ and Eapen, MS and Sohal, SS and Burgess, JK and Hansbro, PM
Keywords: remodelling, extracellular matrix, asthma, COPD, IPF, fibroblasts, collagen, fibrosis, COVID-19
Journal or Publication Title: Pharmacology and Therapeutics
Publisher: Pergamon-Elsevier Science Ltd
ISSN: 0163-7258
DOI / ID Number: 10.1016/j.pharmthera.2021.107839
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© 2021 Elsevier Inc. All rights reserved.

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